Dihalopropene compounds, insecticidal/acaridcidal agents containing same, and intermediates for their production

ABSTRACT

The dihalopropene compounds of the general formula (I) have excellent insecticidal/acaricidal activity, so that they are satisfactorily effective for the control of noxious insects, mites and ticks.

This application is a divisional application Ser. No. 09/864,227, filed on May 25, 2001, now U.S. Pat. No. 6,376,428 which is a divisional application under 37 C.F.R. §1.53(b) of prior application Ser. No. 09/521,119 filed Mar. 7, 2000 (now U.S. Pat. No. 6,268,313); which is a divisional application under 37 C.F.R. §1.53(b) of prior application Ser. No. 09/203,362 filed Dec. 2, 1998 (now U.S. Pat. No. 6,071,861); which is a divisional application under 37 C.F.R. §1.53(b), of prior application Ser. No. 08/809,865 filed May 20, 1997 (now U.S. Pat. No. 5,922,880), and for which priority is claimed under 35 U.S.C. §120. Application Ser. No. 08/809,865 is the national phase of PCT International Application No. PCT/JP95/0208 filed on Oct. 12, 1995 under 35 U.S.C. §37.1. The entire contents of each of the above-identified applications are hereby incorporated by reference. This application also claims priority of Application No. 249296/1954 and 091187/1995 filed in Japan on Oct. 14, 1949 and Apr. 17, 1995, respectively under 35 U.S.C. §119.

TECHNICAL FIELD

The present invention relates to dihalopropene compounds, insecticidal/acaricidal agents containing these compounds as active ingredients, and intermediates for their production.

BACKGROUND ART

As disclosed in JP-A 48-86835/1973 and JP-A 49-1526/1974, for example, it is well known that some kinds of propene compounds can be used as an active ingredient of insecticides.

In view of their insecticidal/acaricidal activity, it cannot always be said that these compounds are satisfactorily effective for the control of noxious insects, mites and ticks.

DISCLOSURE OF INVENTION

The present inventors have intensively studied to find a compound having excellent insecticidal/acaricidal activity. As a result, they have found that particular dihalopropene compounds have satisfactory insecticidal/acaricidal activity for the control of noxious insects, mites and ticks, thereby completing the present invention.

That is, the present invention provides a dihalopropene compound (hereinafter referred to as the present compound) of the general formula:

wherein Z is oxygen, sulfur or NR⁴ (wherein R⁴ is hydrogen or C₁-C₃ alkyl); Y is oxygen, sulfur or NH; X's are independently chlorine or bromine; R², R³ and R¹⁰ are independently halogen, C₁-C₃ haloalkyl or C₁-C₃ alkyl; t is an integer of 0 to 2; and R¹ is Q₁, Q₂, Q₃, Q₄, Q₅, Q₆ or Q₇ of the general formula:

wherein A is an optionally substituted heterocyclic ring group, provided that when A is an optionally substituted heterocyclic ring group containing two oxygen atoms and a condensed benzene ring, A is optionally substituted 1,3-benzodioxolan-2-yl or optionally substituted 1,4-benzodioxan-2-yl; B is oxygen, S(O)_(q), NR⁹, C(═G¹)G² or G¹C(═G²); q is an integer of 0 to 2; R⁹ is hydrogen, acetyl or C₁-C₃ alkyl; G¹ and G² are independently oxygen or sulfur; R⁵, R⁶, R¹¹ and R¹² are independently hydrogen, C₁-C₃ alkyl or trifluoromethyl; R¹³ and R¹⁴ are independently hydrogen, C₁-C₃ alkyl, trifluoromethyl or halogen; p is an integer of 0 to 6; and s is an integer of 1 to 6.

The present invention further provides an insecticidal/acaricidal agent containing the above dihalopropene compound as an active ingredient.

The present invention further provides the following compounds which are useful as intermediates for producing some of the present compounds:

a phenol compound which is 3,5-dichloro-4-(2-(2-(4-chlorophenyl)-1,3-dioxolan-4yl)ethoxy)phenol;

compounds of the general formula:

wherein R⁵, R⁶ and R⁷ are independently hydrogen, C₁-C₃ alkyl or trifluoromethyl; R¹⁵ is halogen, C₁-C₃ alkyl, C₁-C₃ haloalkyl, C₁-C₃ alkoxy or C₁-C₃ haloalkoxy; R², R³ and R¹⁰ are independently halogen, C₁-C₃ alkyl or C₁-C₃ haloalkyl; t is an integer of 0 to 2; u is an integer of 1 to 4; w is an integer of 1 to 4; and B is oxygen, S(O)_(q) or NR⁹ wherein R⁹ is hydrogen, acetyl or C₁-C₃ alkyl and q is an integer of 0 to 2;

compounds of the general formula [I] wherein R⁵, R⁶ and R⁷ are all hydrogen; and R² and R³ are independently halogen or C₁-C₃ alkyl; and

2-(3-methanesulfonyloxypropyloxy)-5-trifluoromethylpyridine.

DETAILED DESCRIPTION OF THE INVENTION

The variables in the above formulae for the present compounds and their intermediates can take the following specific examples.

Examples of the C₁-C₃ alkyl group represented by R², R³, R⁴, R⁵, R⁶, R⁷, R⁹, R¹⁰, R¹¹, R¹², R¹³ or R¹⁴ are methyl, ethyl, n-propyl and isopropyl.

Examples of the halogen atom represented by R¹³ or R¹⁴ are fluorine, chlorine, bromine and iodine.

Examples of the heterocyclic ring in the optionally substituted heterocyclic ring group represented by A are isoxazole, isothiazole, thiazole, 1,3,4-thiadiazole, pyrrole, furan, thiophene, pyrazole, imidazole, 1,2,3-triazole, 1,2,4-triazole, 1,2,3,4-tetrazole, pyridine, pyridazine, pyrimidine, pyrazine, 1,2,4-triazine, 1,3,5-triazine, indole, benzofuran, thianaphthalene, indazole, benzimidazole, benzotriazole, benzisoxazole, benzoxazole, benzothiazole, quinoline, isoquinoline, quinoxaline, quinazole, piperidine, piperazine, tetrahydrofuran, tetrahydropyran, pyrazoline, phthalimide, dioxane, dioxolane and benzodioxolane.

Examples of the substituent on the optionally substituted heterocyclic ring group represented by A are those of the general formula: (R⁸)_(r) (wherein R⁸ is halogen, nitro, cyano, C₁-C₄ alkyl, C₁-C₃ haloalkyl, C₁-C₄ alkoxy, C₁-C₃ haloalkoxy, C₁-C₃ alkylthio, C₁-C₃ haloalkylthio, C₁-C₂ alkylsulfinyl, C₁-C₂ alkylsulfonyl, C₁-C₂ haloalkylsulfinyl, C₁-C₂ haloalkylsulfonyl, C₂-C₄ alkenyl, C₂-C₄ haloalkenyl, C₂-C₄ alkynyl, C₂-C₄ haloalkynyl, amino, dimethylamino, acetamido, acetyl, haloacetyl, formyl, carboxyl, methoxycarbonyl, C₃-C₆ cycloalkyl, (C₁-C₂ alkyl)aminocarbonyl or [di(C₁-C₂ alkyl)amino]carbonyl, or R⁸ is phenyl, benzyl, phenoxy, benzyloxy or pyridyloxy, each of which is optionally substituted with halogen, C₁-C₄ alkyl, C₁-C₃ haloalkyl, C₁-C₄ alkoxy or C₁-C₃ haloalkoxy; and r is an integer of 0 to 7.

Examples of the halogen atom represented by R⁸ or present in R⁸ are fluorine, chlorine, bromine and iodine.

Examples of the C₁-C₄ alkyl group represented by R⁸ or present in R⁸ are methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl and tert-butyl.

Examples of the C₁-C₃ haloalkyl group represented by R⁸ or present in R⁸ are trifluoromethyl, difluoromethyl, bromodifluoromethyl, 2,2,2-trifluoroethyl, 2-fluoroethyl, 2-chloroethyl, 2-bromoethyl, 1-fluoroethyl, 1-chloroethyl, 1-bromoethyl, 2,2,3,3,3-pentafluoropropyl, 3,3,3-trifluoropropyl, 1-fluoropropyl, 2-chloropropyl and 3-bromopropyl.

Examples of the C₁-C₄ alkoxy group represented by R⁸ or present in R⁸ are methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, sec-butoxy, isobutoxy and tert-butoxy.

Examples of the C₁-C₃ haloalkoxy group represented by R⁸ or present in R⁸ are trifluoromethoxy, difluoromethoxy, bromofluoromethoxy, 2-fluoroethoxy, 2,2,2-trifluoroethoxy, 2-chloroethoxy, 2-bromoethoxy, 2-chloro-1,1,2-trifluoroethoxy, 2-bromo-1,1,2-trifluoroethoxy, 1,1,2,2-tetrafluoroethoxy, 1,2,2,3,3,3-hexafluoropropoxy, 3-fluoropropoxy, 3-chloropropoxy, 3-bromopropoxy, 2,2,3,3,3-pentafluoropropoxy, 3,3,3-trifluoropropoxy and 1,1,2,2,2-pentafluoroethoxy.

Examples of the C₁-C₃ alkylthio group represented by R⁸ are methylthio, ethylthio, n-propylthio and isopropylthio.

Examples of the C₁-C₃ haloalkylthio group represented by R⁸ are trifluoromethylthio, difluoromethylthio, bromodifluoromethylthio, 2,2,2-trifluoroethylthio, 2-chloro-1,1,2-trifluoroethylthio, 2-bromo-1,1,2-trifluoroethylthio, 1,1,2,2-tetrafluoroethylthio, 2-chloroethylthio, 2-fluoroethylthio, 2-bromoethylthio, 3-fluoropropylthio, 3-chloropropylthio, (3-bromopropyl)thio, 2,2,3,3,3-pentafluoropropylthio and 3,3,3-trifluoropropylthio.

Examples of the C₁-C₂ alkylsulfinyl group represented by R⁸ are methylsulfinyl and ethylsulfinyl.

Examples of the C₁-C₂ alkylsulfonyl group represented by R⁸ are methylsulfonyl and ethylsulfonyl.

Examples of the C₁-C₂ haloalkylsulfinyl group represented by R⁸ are trifluoromethylsulfinyl, 2,2,2-trifluoroethylsulfinyl and perfluoroethylsulfinyl.

Examples of the C₁-C₂ haloalkylsulfonyl group represented by R⁸ are trifluoromethylsulfonyl, 2,2,2-trifluoroethylsulfonyl and perfluoroethylsulfonyl.

Examples of the C₂-C₄ alkenyl group represented by R⁸ are vinyl, isopropenyl, 1-propenyl, 2-ethyl-1-propenyl, 1-methyl-1-propenyl, allyl, 2-methylpropenyl and 2-butenyl.

Examples of the C₂-C₄ haloalkenyl group represented by R⁸ are 2,2-dichloroethenyl, 2,2-dibromoethenyl, 3,3-dichloroallyl, 3,3-dibromoallyl, 2,3-dichloroallyl, 2,3-dibromoallyl, 2-chloro-2-propenyl, 3-chloro-2-propenyl, 2-bromo-2-propenyl and 3-chloro-2-butenyl.

Examples of the C₂-C₄ alkynyl group represented by R⁸ are ethynyl, 1-propynyl, 2-propynyl and 1-methyl-2-propynyl.

Examples of the C₂-C₄ haloalkynyl group represented by R⁸ are chloroethynyl, bromoethynyl, iodoethynyl, 3-chloro-2-propynyl, 3-bromo-2-propynyl, 3-iodo-2-propynyl, 1-methyl-3-chloro-2-propynyl, 1-methyl-3-bromo-2-propynyl and 1-methyl-3-iodo-2-propynyl.

Examples of the haloacetyl group represented by R⁸ are trifluoromethylacetyl and trichloroacetyl.

Examples of the C₃-C₆ cycloalkyl group represented by R⁸ are cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.

Examples of the C₅-C₆ cycloalkenyl are 1-cyclopentenyl, 2-cyclopentenyl, 3-cyclopentenyl, 1-cyclohexenyl, 2-cyclohexenyl and 3-cyclohexenyl.

Examples of the (C₁-C₂ alkyl)aminocarbonyl group represented by R⁸ are methylaminocarbonyl and ethylamino carbonyl.

Examples of the [di(C₁-C₂ alkyl)amino]carbonyl group represented by R⁸ are dimethylaminocarbonyl, N-methyl-N-ethylaminocarbonyl and diethylaminocarbonyl.

The following are preferred examples of the present compound:

dihalopropene compounds wherein A is a 5- or 6-membered heterocyclic ring group containing at least one oxygen, sulfur or nitrogen and optionally substituted by (R⁸)_(r) (wherein R⁸ is halogen, nitro, cyano, C₁-C₄ alkyl, C₁-C₃ haloalkyl, C₁-C₄ alkoxy, C₁-C₃ haloalkoxy, C₁-C₃ alkylthio, C₁-C₃ haloalkylthio, C₁-C₂ alkylsulfinyl, C₁-C₂ alkylsulfonyl, C₁-C₂ haloalkylsulfinyl, C₁-C₂ haloalkylsulfonyl, C₂-C₄ alkenyl, C₂-C₄ haloalkenyl, C₂-C₄ alkynyl, C₂-C₄ haloalkynyl, amino, dimethylamino, acetamido, acetyl, haloacetyl, formyl, carboxyl, methoxycarbonyl, C₃-C₆ cycloalkyl, (C₁-C₂ alkyl)-aminocarbonyl or [di(C₁-C₂ alkyl)amino]carbonyl, or R⁸ is phenyl, benzyl, phenoxy, benzyloxy or pyridyloxy, each of which is optionally substituted with halogen, C₁-C₄ alkyl, C₁-C₃ haloalkyl, C₁-C₄ alkoxy or C₁-C₃ haloalkoxy; and r is an integer of 0 to 7);

dihalopropene compounds wherein A is 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-thienyl, 3-thienyl, 2-furanyl, 3-furanyl, 5-(1,3-thiazolyl), N-(1,2-dihydro-2-oxo)pyridino, 1,3-dioxolanyl, 1,4-benzodioxanyl, 2-pyrazyl, 2-benzothiazolyl, 2-benzoxazolyl, 2-benzimidazolyl, 2-quinoxalynyl, N-benzimidazolyl, 2-quinolyl, 3-quinolyl or N-phthalimido, each of which is optionally substituted with (R⁸)_(r) (wherein R⁸ and r are each as defined above);

dihalopropene compounds wherein R² and R³ are independently halogen or C₁-C₃ alkyl, and t is 0;

dihalopropene compounds wherein R² and R³ are independently chlorine, bromine, methyl, ethyl or isopropyl, and t is 0;

dihalopropene compounds wherein R² and R³ are both chlorine, and t is 0;

dihalopropene compounds wherein R² is chlorine, R³ is methyl, and t is 0;

dihalopropene compounds wherein R² is ethyl, R³ is methyl, and t is 0;

dihalopropene compounds wherein R² and R³ are both bromine, and t is 0;

dihalopropene compounds wherein R² and R³ are both ethyl, and t is 0;

dihalopropene compounds wherein R² and R³ are independently halogen or C₁-C₃ alkyl, t is 1 or 2, and R¹⁰ is halogen or C₁-C₃ alkyl;

dihalopropene compounds wherein R² and R³ are independently halogen or C₁-C₃ alkyl, t is 1 or 2, and R¹⁰ is halogen;

dihalopropene compounds wherein Y and Z are both oxygen;

dihalopropene compounds wherein R² is Q₁, p is 1 to 6, and A is 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-thienyl, 3-thienyl, 2-furanyl, 3-furanyl, 5-(1,3-thiazolyl), N-(1,2-dihydro-2-oxo)pyridino, 1,3-dioxolanyl or N-phthalimido, each of which is optionally substituted with (R⁸)_(r) (wherein R⁸ and r are each as defined above);

dihalopropene compounds wherein R¹ is Q₁, p is 1 to 6, R⁵, R⁶ and R⁷ are all hydrogen, and A is 1,3-dioxolanyl optionally substituted with (R⁸)_(r) (wherein R⁸ and r are each as defined above);

dihalopropene compounds wherein R¹ is Q₁, p is 1 to 4, R⁵, R⁶ and R⁷ are all hydrogen, and A is 1,3-dioxolanyl optionally substituted with (R⁸)_(r) (wherein R⁸ and r are each as defined above);

dihalopropene compounds wherein R¹ is Q₁, p is 0, and A is 2-pyridyl, 4-pyridyl, 2-thienyl, 3-thienyl, 2-furanyl, 3-furanyl, 5-(1,3-thiazolyl), 1,3-dioxolanyl or 1,4-benzodioxolanyl, each of which is optionally substituted with (R⁸)_(r) (wherein R⁸ and r are each as defined above);

dihalopropene compounds wherein R¹ is Q₂;

dihalopropene compounds wherein R¹ is Q₂, and A is 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-thienyl, 3-thienyl, 2-furanyl, 3-furanyl, 5-(1,3-thiazolyl), 2-pyradyl, 2-benzothiazolyl, 2-benzoxazolyl, 2-benzimidazolyl, 2-quinoxalynyl, N-benzimidazolyl, 2-quinolynyl or 3-quinolyl, each of which is optionally substituted with (R⁸)_(r) (wherein R⁸ and r are each as defined above);

dihalopropene compounds wherein R¹ is Q₂, p is 1 to 4, and A is 2-pyridyl optionally substituted with (R⁸)_(r) (wherein R⁸ and r are each as defined above);

dihalopropene compounds wherein R¹ is Q₂, p is 1 to 4, R⁵, R⁶ and R⁷ are all hydrogen, and A is 2-pyridyl optionally substituted with (R⁸)_(r) (wherein R⁸ and r are each as defined above);

dihalopropene compounds wherein R¹ is Q₂, p is 1 to 4, R⁵, R⁶ and R⁷ are all hydrogen, A is 2-pyridyl optionally substituted with (R⁸)_(r) (wherein R⁸ is halogen or C₁-C₃ haloalkyl and r is as defined above);

dihalopropene compounds wherein R¹ is Q₂, p is 2 or 3, R⁵, R⁶ and R⁷ are all hydrogen, A is 2-pyridyl optionally substituted with (R⁸)_(r) (wherein R⁸ is halogen or C₁-C₃ haloalkyl and r is as defined above);

dihalopropene compounds wherein R¹ is Q₂, p is 2 or 3, R⁵, R⁶ and R⁷ are all hydrogen, A is 2-pyridyl optionally substituted with (R⁸)_(r) (wherein R⁸ is halogen or trifluoromethyl and r is as dined above); and

dihalopropene compounds wherein R¹ is Q₂, p is 2 or 3, R⁵, R⁶ and R⁷ are all hydrogen, B is oxygen, A is 2-pyridyl optionally substituted with (R⁸)_(r) (wherein R⁸ is halogen or trifluoromethyl and r is as defined above).

The following are particularly preferred examples of the present compound. wherein numbers in parentheses are the corresponding compound numbers used below.

(36) 3,5-Dichloro-4-(3-(5-trifluoromethyl-2-pyridyloxy)propyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene;

(47) 3-Ethyl-5-methyl-4-(3-(5-trifluoromethyl-2-pyridyloxy)propyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene; and

(49) 3,5-Dichloro-4-(3-(5-trifluoromethyl-2-pyridylamino)propyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene.

The present compounds can be produced, for example, by the following production processes A-H.

(Production Process A)

In this process, a compound of the general formula:

wherein R¹, R², R³, R¹⁰, t, Y and Z are each as defined above, is reacted with a halide compound of the general formula:

 L—CH₂CH═CX₂  [IV]

wherein X is as defined above and L is halogen (e.g., chlorine, bromine, iodine), mesyloxy or tosyloxy.

The reaction is preferably effected in an inert solvent in the presence of a suitable base.

Examples of the solvent that can be used are ketones such as acetone, methyl ethyl ketone and cyclohexanone; ethers such as 1,2-dimethoxyethane, tetrahydrofuran, dioxane and dialkyl (e.g., C₁-C₄) ether (e.g., diethyl ether, diisopropyl ether); N,N-di-methylformamide, dimethylsulfoxide, hexamethylphosphoric triamide, sulforane, acetonitrile, nitromethane; halogenated hydrocarbons such as dichloromethane, chloroform, 1,2-dichloroethane and chlorobenzene; hydrocarbons such as toluene, benzene and xylene; and water. If necessary, a mixture of these solvents can be used.

Examples of the base which can be used are hydroxides of alkali metals or alkaline earth metals, such as lithium hydroxide, sodium hydroxide, potassium hydroxide and calcium hydroxide; carbonates of alkali metals or alkaline earth metals, such as lithium carbonate, potassium carbonate, sodium carbonate and calcium carbonate; hydrides of alkali metals or alkaline earth metals, such as lithium hydride, sodium hydride, potassium hydride and calcium hydride; alkali metal alkoxides (e.g., C₁-C₄), such as sodium methoxide, sodium ethoxide and potassium tert-butoxide; and organic bases such as triethylamine and pyridine. If necessary, catalysts such as ammonium salts (e.g., triethylbenzylammonium chloride) may be added to the reaction system at a ratio of 0.01 to 1 mole per mole of the compound of the general formula [III].

The reaction temperature is usually set within the range of −20° C. to 150° C. or the boiling point of a solvent used in the reaction, preferably −5° C. to 100° C. or the boiling point of a solvent used in the reaction.

The molar ratio of the starting materials and bases to be used in the reaction can be freely determined, but it is favorable to effect the reaction at an equimolar ratio or a ratio closer thereto.

After completion of the reaction, the reaction mixture is subjected to ordinary post-treatments such as organic solvent extraction and concentration, and the desired compound of the present invention can be isolated. Further, purification can be carried out, if necessary, by an ordinary technique such as chromatography, distillation or recrystallization.

(Production Process B for the present compounds wherein Y is oxygen)

In this process, a compound of the general formula [III] is reacted with an alcohol compound of the general formula:

HO—CH₂CH═CX₂  [V]

wherein X is as defined above.

The reaction is preferably effected in an inert solvent, if necessary, in the presence of a suitable dehydrating agent.

Examples of the dehydrating agent which can be used are dicyclohexylcarbodiimide, and dialkyl (e.g., C₁-C₄) azodicarboxylates (e.g., diethylazodicarboxylate, diisopropylazodicarboxylate)-trialkyl (e.g., C₁-C₂₀) phosphine or triarylphosphine (e.g., triphenylphosphine, trioctylphosphine, tributylphosphine).

Examples of the solvent which can be used are hydrocarbons such as benzene, xylene and toluene; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran and dioxane; and halogenated hydrocarbons such as carbon tetrachloride, dichloromethane, chlorobenzene and dichlorobenzene.

The reaction temperature is usually set within the range of −20° C. to 200° C. or the boiling point of a solvent used in the reaction.

The molar ratio of the starting materials and dehydrating agents to be used in the reaction can be freely determined, but it is favorable to effect the reaction at an equimolar ratio or a ratio closer thereto.

After completion of the reaction, the reaction mixture is subjected to ordinary post-treatments such as organic solvent extraction and concentration, and the desired compound of the present invention can be isolated. Further, purification can be carried out by an ordinary technique such as chromatography, distillation or recrystallization.

(Production Process C for the present compounds wherein Y is oxygen)

In this process, an aldehyde compound of the general formula:

wherein R¹, R², R³, R¹⁰, t and Z are each as defined above, is reacted with carbon tetrachloride or carbon tetrabromide.

The reaction is preferably effected in an inert solvent in the presence of a suitable trialkylphosphine or triarylphosphine, and if necessary, in the presence of metal zinc.

Examples of the solvent which can be used are hydrocarbons such as benzene, xylene and toluene; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran and dioxane; and halogenated hydrocarbons (exclusive of carbon tetrabromide and carbon tetrachloride) such as dichloromethane, 1,2-dichloroethane and chlorobenzene.

The reaction temperature is usually set within the range of −30° C. to 150° C. or the boiling point of a solvent used in the reaction.

Examples of the trialkyl (e.g., C₁-C₂₀) phosphine or triarylphosphine are triphenylphosphine and trioctylphosphine. The metal zinc which is used, if necessary, is preferably in dust form.

The molar ratio of the starting materials and reagents to be used in the reaction can be freely determined, but the ratio is preferably such that carbon tetrabromide or tetrachloride, trialkylphosphine or triarylphosphine, and zinc are 2 moles, 2 or 4 moles (2 moles when zinc is used), and 2 moles, respectively, per mole of the aldehyde compound of the general formula [VI], or it is favorable to effect the reaction at a ratio closer thereto.

After completion of the reaction, the reaction mixture is subjected to ordinary post-treatments such as organic solvent extraction and concentration, and the desired compound of the present invention can be isolated. Further, purification can be carried out by an ordinary technique such as chromatography, distillation or recrystallization.

(Production Process D for the present compounds wherein Y and Z are both oxygen)

In this process, a compound of the general formula:

wherein R², R³, R¹⁰, t and X are each as defined above, is reacted with a compound of the general formula:

R¹—L  [VIII]

wherein R¹ and L are each as defined above.

The reaction is preferably effected in an inert solvent in the presence of a suitable base.

Examples of the solvent which can be used are ketones such as acetone, methyl ethyl ketone and cyclohexanone; ethers such as 1,2-dimethoxyethane, tetrahydrofuran, dioxane and dialkyl (e.g., C₁-C₄) ethers (e.g., diethyl ether, diisopropyl ether); N,N-dimethylformamide, dimethylsulfoxide, hexamethylphosphoric triamide, sulforane, acetonitrile, nitromethane; halogenated hydrocarbons such as dichloromethane, chloroform, 1,2-dichloroethane and chlorobenzene; hydrocarbons such as toluene, benzene and xylene; and water. If necessary, a mixture of these solvents can be used.

Examples of the base which can be used are hydroxides of alkali metals or alkaline earth metals, such as lithium hydroxide, sodium hydroxide, potassium hydroxide and calcium hydroxide; carbonates of alkali metals or alkaline earth metals, such as lithium carbonate, potassium carbonate, sodium carbonate and calcium carbonate; hydrides of alkali metals or alkaline earth metals, such as lithium hydride, sodium hydride, potassium hydride and calcium hydride; alkali metal alkoxides (e.g., C₁-C₄) such as sodium methoxide, sodium ethoxide and potassium tert-butoxide; organic bases such as triethylamine and pyridine. If necessary, catalysts such as ammonium salts (e.g., triethylbenzylammonium chloride) may be added to the reaction system at a ratio of 0.01 to 1 mole per mole of the compound of the general formula [VII].

The reaction temperature is usually set within the range of −20° C. to 150° C. or the boiling point of a solvent used in the reaction, preferably −5° C. to 100° C. or the boiling point of a solvent used in the reaction.

The molar ratio of the starting materials and dehydrating agents to be used in the reaction can be freely determined, but it is favorable to effect the reaction at an equimolar ratio or a ratio closer thereto.

After completion of the reaction, the reaction mixture is subjected to ordinary post-treatments such as organic solvent extraction and concentration, and the desired compound of the present invention can be isolated. Further, purification can be carried out by an ordinary technique such as chromatography, distillation or recrystallization.

(Production Process E for the present compounds wherein Y and Z are both oxygen)

In this process, a compound of the general formula [VII] is reacted with an alcohol compound of the general formula:

 R¹—OH  [IX]

wherein R¹ is as defined above.

The reaction is preferably effected in an inert solvent, if necessary, in the presence of a suitable dehydrating agent.

Examples of the dehydrating agent which can be used are dicyclohexylcarbodiimide, and dialkyl (e.g., C₁-C₄) azodicarboxylates (e.g., diethylazodicarboxylate, diisopropylazodicarboxylate)-trialkyl (e.g., C₁-C₂₀) phosphine or triarylphosphine (e.g., triphenylphosphine, trioctylphosphine, tributylphosphine).

Examples of the solvent which can be used are hydrocarbons such as benzene, xylene and toluene; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran and dioxane; and halogenated hydrocarbons such as carbon tetrachloride, dichloromethane, chlorobenzene and dichlorobenzene.

The reaction temperature is usually set within the range of −20° C. to 200° C. or the boiling point of a solvent used in the reaction.

The molar ratio of the materials and dehydrating agents to be used in the reaction can be freely determined, but it is favorable to effect the reaction at an equimolar ratio or a ratio closer thereto.

After completion of the reaction, the reaction mixture is subjected to ordinary post-treatments such as organic solvent extraction and concentration, and the desired compound of the present invention can be isolated. Further, purification can be carried out by an ordinary technique such as chromatography, distillation or recrystallization.

(Production Process F for the present compounds wherein Y and Z are both oxygen, R¹ is Q₂ or Q₃, and B is B¹ (wherein B ¹ is oxygen, sulfur or NR⁹ [wherein R⁹ is as defined above]))

In this process, a compound of the general formula:

wherein B¹, R², R³, R⁵, R⁶, R⁷, R¹⁰, p, t and X are each as defined above, is reacted with a compound of the general formula:

wherein A, R¹¹, R¹², L and s are each as defined above.

The reaction is preferably effected in an inert solvent in the presence of a suitable base.

Examples of the solvent which can be used are ketones such as acetone, methyl ethyl ketone and cyclohexanone; ethers such as 1,2-dimethoxyethane, tetrahydrofuran, dioxane and dialkyl (e.g., C₁-C₄) ethers (e.g., diethyl ether, diisopropyl ether); N,N-dimethylformamide, dimethylsulfoxide, hexamethylphosphoric triamide, sulforane, acetonitrile, nitromethane; halogenated hydrocarbons such as dichloromethane, chloroform, 1,2-dichloroethane and chlorobenzene; hydrocarbons such as toluene, benzene and xylene; and water. If necessary, a mixture of these solvents can be used.

Examples of the base which can be used are hydroxides of alkali metals or alkaline earth metals, such as lithium hydroxide, sodium hydroxide, potassium hydroxide and calcium hydroxide; carbonates of alkali metals or alkaline earth metals, such as lithium carbonate, potassium carbonate, sodium carbonate and calcium carbonate; hydrides of alkali metals or alkaline earth metals, such as lithium hydride, sodium hydride, potassium hydride and calcium hydride; alkali metal alkoxides (e.g., C₁-C₄) such as sodium methoxide, sodium ethoxide and potassium tert-butoxide; organic bases such as triethylamine and pyridine. If necessary, catalysts such as ammonium salts (e.g., triethylbenzylammonium chloride) may be added to the reaction system at a ratio of 0.01 to 1 mole per mole of the compound of the general formula [X].

The reaction temperature is usually set within the range of −20° C. to 150° C. or the boiling point of a solvent used in the reaction, preferably −5° C. to 100° C. or the boiling point of a solvent used in the reaction.

The molar ratio of the starting materials and dehydrating agents to be used in the reaction can be freely determined, but it is favorable to effect the reaction at an equimolar ratio or a ratio closer thereto.

After completion of the reaction, the reaction mixture is subjected to ordinary post-treatments such as organic solvent extraction and concentration, and the desired compound of the present invention can be isolated. Further, purification can be carried out by an ordinary technique such as chromatography, distillation or recrystallization.

(Production Process G for the present compounds wherein Y, Z and B are all oxygen and R¹ is Q₂, Q₃, Q₆ or Q₇)

In this process, an alcohol compound of the general formula:

wherein R², R³, R¹⁰, R⁵, R⁶, R⁷, p, t and X are each as defined above, is reacted with compound Q₂₁, Q₃₁, Q₆₁ or Q₇₁ of the general formula:

wherein R¹¹, R¹², R¹³, R¹⁴ A and s are each as defined above.

The reaction is preferably effected in an inert solvent, if necessary, in the presence of a suitable dehydrating agent.

Examples of the dehydrating agent which can be used are dicyclohexylcarbodiimide, and dialkyl (e.g., C₁-C₄) azodicarboxylates (e.g., diethylazodicarboxylate, diisopropylazodicarboxylate)-trialkyl (e.g., C₁-C₂₀) phosphine or triarylphosphine (e.g., triphenylphosphine, trioctylphosphine, tributylphosphine).

Examples of the solvent which can be used are hydrocarbons such as benzene, xylene and toluene; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran and dioxane; and halogenated hydrocarbons such as carbon tetrachloride, dichloromethane, chlorobenzene and dichlorobenzene.

The reaction temperature is usually set within the range of −20° C. to 200° C. or the boiling point of a solvent used in the reaction.

The molar ratio of the materials and dehydrating agents to be used in the reaction can be freely determined, but it is favorable to effect the reaction at an equimolar ratio or a ratio closer thereto.

After completion of the reaction, the reaction mixture is subjected to ordinary post-treatments such as organic solvent extraction and concentration, and the desired compound of the present invention can be isolated. Further, purification can be carried out by an ordinary technique such as chromatography, distillation or recrystallization.

(Production Process H for the present compounds wherein Y and Z are both oxygen and R¹ is Q₂, Q₃, Q₆ or Q₇)

In this process, a compound of the general formula:

wherein R², R³, R⁵, R⁶, R⁷, R¹⁰, X, L, p and t are each as defined above, is reacted with compound Q₂₂, Q₃₂, Q₆₂ or Q₇₂ of the general formula:

wherein R¹¹, R¹², R¹³, R¹⁴, A, B and s are each as defined above.

The reaction is preferably effected in an inert solvent in the presence of a suitable base.

Examples of the solvent which can be used are ketones such as acetone, methyl ethyl ketone and cyclohexanone; ethers such as 1,2-dimethoxyethane, tetrahydrofuran, dioxane and dialkyl (e.g., C₁-C₄) ethers (e.g., diethyl ether, diisopropyl ether); N,N-dimethylformamide, dimethylsulfoxide, hexamethylphosphoric triamide, sulforane, acetonitrile, nitromethane; halogenated hydrocarbons such as dichloromethane, chloroform, 1,2-dichloroethane and chlorobenzene; hydrocarbons such as toluene, benzene and xylene; and water. If necessary, a mixture of these solvents can be used.

Examples of the base which can be used are hydroxides of alkali metals or alkaline earth metals, such as lithium hydroxide, sodium hydroxide, potassium hydroxide and calcium hydroxide; carbonates of alkali metals or alkaline earth metals, such as lithium carbonate, potassium carbonate, sodium carbonate and calcium carbonate; hydrides of alkali metals or alkaline earth metals, such as lithium hydride, sodium hydride, potassium hydride and calcium hydride; alkali metal alkoxides (e.g., C₁-C₄) such as sodium methoxide, sodium ethoxide and potassium tert-butoxide; organic bases such as triethylamine and pyridine. If necessary, catalysts such as ammonium salts (e.g., triethylbenzylammonium chloride) may be added to the reaction system at a ratio of 0.01 to 1 mole per mole of the compound of the general formula [XIV].

The reaction temperature is usually set within the range of −20° C. to 150° C. or the boiling point of a solvent used in the reaction, preferably −5° C. to 100° C. or the boiling point of a solvent used in the reaction.

The molar ratio of the starting materials and dehydrating agents to be used in the reaction can be freely determined, but it is favorable to effect the reaction at an equimolar ratio or a ratio closer thereto.

After completion of the reaction, the reaction mixture is subjected to ordinary post-treatments such as organic solvent extraction and concentration, and the desired compound of the present invention can be isolated. Further, purification can be carried out by an ordinary technique such as chromatography, distillation or recrystallization.

When the present compound has an asymmetry carbon atom, it is to be construed to include its optically active isomers ((+)-form and (−)-form) having biological activity and their mixtures at any ratio. When the present compound exhibits geometrical isomerism, it is to be construed to include its geometrical isomers (cis-form and transform) and their mixtures at any ratio.

The following are typical examples of the present compound (wherein R¹ is as shown in Tables 1 to 46), which are not to be construed to limit the scope of the present invention.

TABLE 1

Bonding position of heterocyclic ring R⁵ R⁶ R⁷ p (R⁸)_(r) 2 H H H 0 H 2 H H H 1 H 2 H H H 2 H 2 H H H 3 H 2 H H H 4 H 2 H H H 5 H 2 H H H 6 H 2 H H H 0 5-CH₃ 2 H H H 1 5-CH₃ 2 H H H 2 5-CH₃ 2 H H H 3 5-CH₃ 2 H H H 4 5-CH₃ 2 H H H 5 5-CH₃ 2 H H H 6 5-CH₃ 2 H H H 0 5-CH₂OCH₃ 2 H H H 1 5-CH₂OCH₃ 2 H H H 2 5-CH₂OCH₃ 2 H H H 3 5-CH₂OCH₃ 2 H H H 4 5-CH₂OCH₃ 2 H H H 0 5-CH₂CH₃ 2 H H H 1 5-CH₂CH₃ 2 H H H 2 5-CH₂CH₃ 2 H H H 3 5-CH₂CH₃ 2 H H H 4 5-CH₂CH₃ 2 H H H 5 5-CH₂CH₃ 2 H H H 6 5-CH₂CH₃ 2 H H CH₃ 0 H 2 H H CH₃ 0 5-CH₃ 2 H H H 0 5-CHO 2 H H H 1 5-CHO 2 H H H 2 5-CHO 2 H H H 3 5-CHO 2 H H H 4 5-CHO 2 H H H 5 5-CHO 2 H H H 6 5-CHO 2 H H H 0 5-NO₂ 2 H H H 1 5-NO₂ 2 H H H 2 5-NO₂ 2 H H H 3 5-NO₂ 2 H H H 4 5-NO₂ 2 H H H 5 5-NO₂ 2 H H H 6 5-NO₂ 2 H H H 0 3-CO₂CH₃ 3 H H H 0 H 3 H H H 1 H 3 H H H 2 H 3 H H H 3 H 3 H H H 4 H 3 H H H 5 H 3 H H H 6 H 3 H H H 0 2-CH₃ 3 H H H 1 2-CH₃ 3 H H H 2 2-CH₃ 3 H H H 3 2-CH₃ 3 H H H 4 2-CH₃ 3 H H H 5 2-CH₃ 3 H H H 6 2-CH₃ 3 H H H 0 2,5-(CH₃)₂ 3 H H H 1 2,5-(CH₃)₂ 3 H H H 2 2,5-(CH₃)₂ 3 H H H 3 2,5-(CH₃)₂ 3 H H H 4 2,5-(CH₃)₂ 3 H H H 5 2,5-(CH₃)₂ 3 H H H 6 2,5-(CH₃)₂ 3 H H H 0 2,4-(CH₃)₂ 3 H H H 1 2,4-(CH₃)₂ 3 H H H 2 2,4-(CH₃)₂ 3 H H H 3 2,4-(CH₃)₂ 3 H H H 4 2,4-(CH₃)₂ 3 H H H 5 2,4-(CH₃)₂ 3 H H H 6 2,4-(CH₃)₂

TABLE 2

Bonding position of heterocyclic ring R⁵ R⁶ R⁷ p (R⁸)_(r) B 2 H H H 1 H COO 2 H H H 2 H COO 2 H H H 3 H COO 2 H H H 1 5-CH₃ COO 2 H H H 1 5-C₂H₅ COO 2 H H H 1 5-Br COO 2 H H H 2 5-CH₃ COO 2 H H H 2 5-C₂H₅ COO 2 H H H 2 5-Br COO 2 H H H 3 5-CH₃ COO 2 H H H 3 5-C₂H₅ COO 2 H H H 3 5-CH₃ COO 3 H H H 1 H COO 3 H H H 2 H COO 3 H H H 3 H COO

TABLE 3

Bonding position of heterocyclic ring R⁵ R⁶ R⁷ p (R⁸)_(r) 2 H H H 0 H 2 H H H 1 H 2 H H H 2 H 2 H H H 3 H 2 H H H 4 H 2 H H H 5 H 2 H H H 6 H 2 H H H 0 5-CH₃ 2 H H H 1 5-CH₃ 2 H H H 2 5-CH₃ 2 H H H 3 5-CH₃ 2 H H H 4 5-CH₃ 2 H H H 5 5-CH₃ 2 H H H 6 5-CH₃ 2 H H H 0 5-Cl 2 H H H 1 5-Cl 2 H H H 2 5-Cl 2 H H H 3 5-Cl 2 H H H 4 5-Cl 2 H H H 5 5-Cl 2 H H H 6 5-Cl 2 H H H 0 5-Br 2 H H H 1 5-Br 2 H H H 2 5-Br 2 H H H 3 5-Br 2 H H H 4 5-Br 2 H H H 5 5-Br 2 H H H 6 5-Br 2 H H H 0 5-NO₂ 2 H H H 1 5-NO₂ 2 H H H 2 5-NO₂ 2 H H H 3 5-NO₂ 2 H H H 4 5-NO₂ 2 H H H 5 5-NO₂ 2 H H H 6 5-NO₂ 2 H H H 0 5-NH₂ 2 H H H 1 5-NH₂ 2 H H H 2 5-NH₂ 2 H H H 3 5-NH₂ 2 H H H 4 5-NH₂ 2 H H H 5 5-NH₂ 2 H H H 6 5-NH₂ 2 H H H 0 5-NHCOCH₃ 2 H H H 1 5-NHCOCH₃ 2 H H H 2 5-NHCOCH₃ 2 H H H 3 5-NHCOCH₃ 2 H H H 4 5-NHCOCH₃ 2 H H H 5 5-NHCOCH₃ 2 H H H 6 5-NHCOCH₃ 2 H H H 0 5-NHCOCF₃ 2 H H H 1 5-NHCOCF₃ 2 H H H 2 5-NHCOCF₃ 2 H H H 3 5-NHCOCF₃ 2 H H H 4 5-NHCOCF₃ 2 H H H 5 5-NHCOCF₃ 2 H H H 6 5-NHCOCF₃ 2 H H CH₃ 0 3-CH₃ 2 H H CH₃ 0 5-Cl 2 H H CH₃ 0 5-Br 2 H H CH₂CH₃ 0 H 2 H H H 0 3-CH₃ 2 H H H 1 3-CH₃ 2 H H H 0 5-NH₂ 2 H H H 2 3-CH₃ 2 H H H 3 3-CH₃ 2 H H H 4 3-CH₃ 2 H H H 5 3-CH₃ 2 H H H 6 3-CH₃ 2 H H H 0 4-Br 2 H H H 1 4-Br 2 H H H 2 4-Br 2 H H H 3 4-Br 2 H H H 4 4-Br 2 H H H 5 4-Br 2 H H H 6 4-Br 3 H H H 0 H 3 H H H 1 H 3 H H H 2 H 3 H H H 3 H 3 H H H 4 H 3 H H H 5 H 3 H H H 6 H 3 H H CH₃ 0 H 3 H H CH₃ 0 2,5-(CH₃)₂

TABLE 4

Bonding position of heterocyclic ring B R⁵ R⁶ R⁷ p (R⁸)_(r) F 3 S H H H 0 2-CH₃ O 2 SO₂ H H H 0 H S 2 SO₂ H H H 1 H S 2 SO₂ H H H 2 H S 2 SO₂ H H H 3 H S 2 SO₂ H H H 4 H S 2 SO₂ H H H 5 H S 2 SO₂ H H H 6 H S 2 COO H H H 2 H S 2 COO H H H 3 H S 2 COO H H H 4 H S 3 COO H H H 2 H S 3 COO H H H 3 H S 3 COO H H H 4 H S 2 COO H H H 2 5-CH₃ S 2 COO H H H 3 5-CH₃ S 2 COO H H H 4 5-CH₃ S

TABLE 5

Bonding position of heterocyclic ring R⁵ R⁶ R⁷ p (R⁸)_(r) 2 H H H 0 H 2 H H H 1 H 2 H H H 2 H 2 H H H 3 H 2 H H H 4 H 2 H H H 5 H 2 H H H 6 H

TABLE 6

Bonding position of heterocyclic ring R⁵ R⁶ R⁷ p (R⁸)_(r) 2 H H H 0 H 2 H H H 1 H 2 H H H 2 H 2 H H H 3 H 2 H H H 4 H 2 H H H 5 H 2 H H H 6 H

TABLE 7

Bonding position of heterocyclic ring R⁵ R⁶ R⁷ p (R⁸)_(r) 3 H H H 0 H 3 H H H 1 H 3 H H H 2 H 3 H H H 3 H 3 H H H 4 H 3 H H H 5 H 3 H H H 6 H 3 H H H 0 5-Cl 3 H H H 1 5-Cl 3 H H H 2 5-Cl 3 H H H 3 5-Cl 3 H H H 4 5-Cl 3 H H H 5 5-Cl 3 H H H 6 5-Cl 3 H H H 0 5-Br 3 H H H 1 5-Br 3 H H H 2 5-Br 3 H H H 3 5-Br 3 H H H 4 5-Br 3 H H H 5 5-Br 3 H H H 6 5-Br 5 H H H 0 H 5 H H H 1 H 5 H H H 2 H 5 H H H 3 H 5 H H H 4 H 5 H H H 5 H 5 H H H 6 H 5 H H H 0 3-Cl 5 H H H 1 3-Cl 5 H H H 2 3-Cl 5 H H H 3 3-Cl 5 H H H 4 3-Cl 5 H H H 5 3-Cl 5 H H H 6 3-Cl 5 H H H 0 3-Br 5 H H H 1 3-Br 5 H H H 2 3-Br 5 H H H 3 3-Br 5 H H H 4 3-Br 5 H H H 5 3-Br 5 H H H 6 3-Br 4 H H H 0 H 4 H H H 1 H 4 H H H 2 H 4 H H H 3 H 4 H H H 4 H 4 H H H 5 H 4 H H H 6 H 4 H H H 0 3, 5-(CH₃)₂

TABLE 8

Bonding position of heterocyclic ring R⁵ R⁶ R⁷ p (R⁸)_(r) 3 H H H 0 H 3 H H H 1 H 3 H H H 2 H 3 H H H 3 H 3 H H H 4 H 3 H H H 5 H 3 H H H 6 H 3 H H H 0 5-Cl 3 H H H 1 5-Cl 3 H H H 2 5-Cl 3 H H H 3 5-Cl 3 H H H 4 5-Cl 3 H H H 5 5-Cl 3 H H H 6 5-Cl 3 H H H 0 5-Br 3 H H H 1 5-Br 3 H H H 2 5-Br 3 H H H 3 5-Br 3 H H H 4 5-Br 3 H H H 5 5-Br 3 H H H 6 5-Br

TABLE 9

Bonding position of heterocyclic ring R⁵ R⁶ R⁷ p (R⁸)_(r) 4 H H H 0 H 4 H H H 1 H 4 H H H 2 H 4 H H H 3 H 4 H H H 4 H 4 H H H 5 H 4 H H H 6 H 4 H H H 0 2-Cl 4 H H H 1 2-Cl 4 H H H 2 2-Cl 4 H H H 3 2-Cl 4 H H H 4 2-Cl 4 H H H 5 2-Cl 4 H H H 6 2-Cl 4 H H H 0 2-Br 4 H H H 1 2-Br 4 H H H 2 2-Br 4 H H H 3 2-Br 4 H H H 4 2-Br 4 H H H 5 2-Br 4 H H H 6 2-Br 5 H H H 0 H 5 H H H 1 H 5 H H H 2 H 5 H H H 3 H 5 H H H 4 H 5 H H H 5 H 5 H H H 6 H 5 H H H 0 2-Cl 5 H H H 1 2-Cl 5 H H H 2 2-Cl 5 H H H 3 2-Cl 5 H H H 4 2-Cl 5 H H H 5 2-Cl 5 H H H 6 2-Cl 5 H H H 0 2-Br 5 H H H 1 2-Br 5 H H H 2 2-Br 5 H H H 3 2-Br 5 H H H 4 2-Br 5 H H H 5 2-Br 5 H H H 6 2-Br 5 H H H 1 4-CH₃ 5 H H CH₃ 0 4-CH₃ 2 H H CH₃ 0 H

TABLE 10

Bonding position of heterocyclic ring R⁵ R⁶ R⁷ p (R⁸)_(r) 1 H H H 0 H 1 H H H 1 H 1 H H H 2 H 1 H H H 3 H 1 H H H 4 H 1 H H H 5 H 1 H H H 6 H 1 H H H 0 2-CH₂CH₃ 1 H H H 1 2-CH₂CH₃ 1 H H H 2 2-CH₂CH₃ 1 H H H 3 2-CH₂CH₃ 1 H H H 4 2-CH₂CH₃ 1 H H H 5 2-CH₂CH₃ 1 H H H 6 2-CH₂CH₃ 1 H H H 0 2,5-(CH₃)₂ 1 H H H 1 2,5-(CH₃)₂ 1 H H H 2 2,5-(CH₃)₂ 1 H H H 3 2,5-(CH₃)₂ 1 H H H 4 2,5-(CH₃)₂ 1 H H H 5 2,5-(CH₃)₂ 1 H H H 6 2,5-(CH₃)₂ 1 H H H 0 2,4-(CH₃)₂, 3-CH₂CH₃ 1 H H H 1 2,4-(CH₃)₂, 3-CH₂CH₃ 1 H H H 2 2,4-(CH₃)₂, 3-CH₂CH₃ 1 H H H 3 2,4-(CH₃)₂, 3-CH₂CH₃ 1 H H H 4 2,4-(CH₃)₂, 3-CH₂CH₃ 1 H H H 5 2,4-(CH₃)₂, 3-CH₂CH₃ 1 H H H 6 2,4-(CH₃)₂, 3-CH₂CH₃ 1 H H H 0 2,4-(CH₃)₂, 3-COCH₃ 1 H H H 1 2,4-(CH₃)₂, 3-COCH₃ 1 H H H 2 2,4-(CH₃)₂, 3-COCH₃ 1 H H H 3 2,4-(CH₃)₂, 3-COCH₃ 1 H H H 4 2,4-(CH₃)₂, 3-COCH₃ 1 H H H 5 2,4-(CH₃)₂, 3-COCH₃ 1 H H H 6 2,4-(CH₃)₂, 3-COCH₃ 1 H H H 0 2-COCH₃ 1 H H H 1 2-COCH₃ 1 H H H 2 2-COCH₃ 1 H H H 3 2-COCH₃ 1 H H H 4 2-COCH₃ 1 H H H 5 2-COCH₃ 1 H H H 6 2-COCH₃ 1 H H H 0 2-CHO 1 H H H 1 2-CHO 1 H H H 2 2-CHO 1 H H H 3 2-CHO 1 H H H 4 2-CHO 1 H H H 5 2-CHO 1 H H H 6 2-CHO 2 H H CH₃ 0 2,4-(CH₃)₂ 2 H H CH₃ 0 H 2 H H CH₃ 0 1-CH₃ 3 H H CH₃ 0 1-CH₃ 3 H H H 0 H 3 H H H 1 H 3 H H H 2 H 3 H H H 3 H 3 H H H 4 H 3 H H H 5 H 3 H H H 6 H 2 H H H 0 H 2 H H H 1 1-CH₃ 2 H H H 2 1-CH₃ 2 H H H 3 1-CH₃ 2 H H H 4 1-CH₃ 2 H H H 5 1-CH₃ 2 H H H 6 1-CH₃ 2 H H H 0 3,5-(CH₃)₂ 2 H H H 1 3,5-(CH₃)₂ 2 H H H 2 3,5-(CH₃)₂ 2 H H H 3 3,5-(CH₃)₂ 2 H H H 4 3,5-(CH₃)₂ 2 H H H 5 3,5-(CH₃)₂ 2 H H H 6 3,5-(CH₃)₂ 2 H H H 0 3,4,5-(CH₃)₃ 2 H H H 1 3,4,5-(CH₃)₃ 2 H H H 2 3,4,5-(CH₃)₃ 2 H H H 3 3,4,5-(CH₃)₃ 2 H H H 4 3,4,5-(CH₃)₃ 2 H H H 5 3,4,5-(CH₃)₃ 2 H H H 6 3,4,5-(CH₃)₃ 2 H H H 0 3,4-(C₂H₅)₂, 5-CH₃ 2 H H H 1 3,4-(C₂H₅)₂, 5-CH₃ 2 H H H 2 3,4-(C₂H₅)₂, 5-CH₃ 2 H H H 3 3,4-(C₂H₅)₂, 5-CH₃ 2 H H H 4 3,4-(C₂H₅)₂, 5-CH₃ 2 H H H 5 3,4-(C₂H₅)₂, 5-CH₃ 2 H H H 6 3,4-(C₂H₅)₂, 5-CH₃

TABLE 11

Bonding position of heterocyclic ring r⁵ R⁶ R⁷ p (R⁸)_(r) 2 H H H 0 5-Cl 2 H H H 1 5-Cl 2 H H H 2 5-Cl 2 H H H 3 5-Cl 2 H H H 4 5-Cl 2 H H H 5 5-Cl 2 H H H 6 5-Cl 2 H H H 0 5-Br 2 H H H 1 5-Br 2 H H H 2 5-Br 2 H H H 3 5-Br 2 H H H 4 5-Br 2 H H H 5 5-Br 2 H H H 6 5-Br 2 H H H 0 5-Cl 2 H H H 1 5-Cl 2 H H H 2 5-Cl 2 H H H 3 5-Cl 2 H H H 4 5-Cl 2 H H H 5 5-Cl 2 H H H 6 5-Cl 2 H H H 0 5-Br 2 H H H 1 5-Br 2 H H H 2 5-Br 2 H H H 3 5-Br 2 H H H 4 5-Br 2 H H H 5 5-Br 2 H H H 6 5-Br

TABLE 12

Bonding position of heterocyclic ring B R⁵ R⁶ R⁷ p (R⁸) r 2 O H H H 0 5-CH₃ 2 O H H H 1 5-CH₃ 2 O H H H 2 5-CH₃ 2 O H H H 3 5-CH₃ 2 O H H H 4 5-CH₃ 2 O H H H 5 5-CH₃ 2 O H H H 6 5-CH₃ 2 O H H H 0 5-CF₃ 2 O H H H 1 5-CF₃ 2 O H H H 2 5-CF₃ 2 O H H H 3 5-CF₃ 2 O H H H 4 5-CF₃ 2 O H H H 5 5-CF₃ 2 O H H H 6 5-CF₃ 2 O H H H 0 5-Cl 2 O H H H 1 5-Cl 2 O H H H 2 5-Cl 2 O H H H 3 5-Cl 2 O H H H 4 5-Cl 2 O H H H 5 5-Cl 2 O H H H 6 5-Cl 2 O H H H 0 5-Br 2 O H H H 1 5-Br 2 O H H H 2 5-Br 2 O H H H 3 5-Br 2 O H H H 4 5-Br 2 O H H H 5 5-Br 2 O H H H 6 5-Br 2 S H H H 0 5-CH₃ 2 S H H H 1 5-CH₃ 2 S H H H 2 5-CH₃ 2 S H H H 3 5-CH₃ 2 S H H H 4 5-CH₃ 2 S H H H 5 5-CH₃ 2 S H H H 6 5-CH₃ 2 S H H H 0 5-CF₃ 2 S H H H 1 5-CF₃ 2 S H H H 2 5-CF₃ 2 S H H H 3 5-CF₃ 2 S H H H 4 5-CF₃ 2 S H H H 5 5-CF₃ 2 S H H H 6 5-CF₃ 2 S H H H 0 5-Cl 2 S H H H 1 5-Cl 2 S H H H 2 5-Cl 2 S H H H 3 5-Cl 2 S H H H 4 5-Cl 2 S H H H 5 5-Cl 2 S H H H 6 5-Cl 2 S H H H 0 5-Br 2 S H H H 1 5-Br 2 S H H H 2 5-Br 2 S H H H 3 5-Br 2 S H H H 4 5-Br 2 S H H H 5 5-Br 2 S H H H 6 5-Br

TABLE 13

Bonding position of heterocyclic ring R⁵ R⁶ R⁷ p (R⁸) r 1 H H H 0 H 1 H H H 1 H 1 H H H 2 H 1 H H H 3 H 1 H H H 4 H 1 H H H 5 H 1 H H H 6 H 1 H H H 0 3-CH₃ 1 H H H 1 3-CH₃ 1 H H H 2 3-CH₃ 1 H H H 3 3-CH₃ 1 H H H 4 3-CH₃ 1 H H H 5 3-CH₃ 1 H H H 6 3-CH₃ 1 H H H 0 4-CH₃ 1 H H H 1 4-CH₃ 1 H H H 2 4-CH₃ 1 H H H 3 4-CH₃ 1 H H H 4 4-CH₃ 1 H H H 5 4-CH₃ 1 H H H 6 4-CH₃ 1 H H H 0 4-Br 1 H H H 1 4-Br 1 H H H 2 4-Br 1 H H H 3 4-Br 1 H H H 4 4-Br 1 H H H 5 4-Br 1 H H H 6 4-Br 1 H H H 0 4-I 1 H H H 1 4-I 1 H H H 2 4-I 1 H H H 3 4-I 1 H H H 4 4-I 1 H H H 5 4-I 1 H H H 6 4-I 1 H H H 0 3,5-(CH₃)₂ 1 H H H 1 3,5-(CH₃)₂ 1 H H H 2 3,5-(CH₃)₂ 1 H H H 3 3,5-(CH₃)₂ 1 H H H 4 3,5-(CH₃)₂ 1 H H H 5 3,5-(CH₃)₂ 1 H H H 6 3,5-(CH₃)₂ 1 H H H 0 3-CH₃, 4-Br 1 H H H 1 3-CH₃, 4-Br 1 H H H 2 3-CH₃, 4-Br 1 H H H 3 3-CH₃, 4-Br 1 H H H 4 3-CH₃, 4-Br 1 H H H 5 3-CH₃, 4-Br 1 H H H 6 3-CH₃, 4-Br 1 H H H 0 3,5-(CH₃)₂, 4-Br 1 H H H 1 3,5-(CH₃)₂, 4-Br 1 H H H 2 3,5-(CH₃)₂, 4-Br 1 H H H 3 3,5-(CH₃)₂, 4-Br 1 H H H 4 3,5-(CH₃)₂, 4-Br 1 H H H 5 3,5-(CH₃)₂, 4-Br 1 H H H 6 3,5-(CH₃)₂, 4-Br 4 H H H 0 H

TABLE 14

Bonding position of heterocyclic ring B R⁵ R⁶ R⁷ p (R⁸) r 4 NH H H H 0 5-CH₃, 1-CH₃, 2-C₆H₅ 5 NH H H H 0 1-CH₂CH₃ 5 NH H H H 1 1-CH₂CH₃ 5 NH H H H 2 1-CH₂CH₃ 5 NH H H H 3 1-CH₂CH₃ 5 NH H H H 4 1-CH₂CH₃ 5 NH H H H 5 1-CH₂CH₃ 5 NH H H H 6 1-CH₂CH₃

TABLE 15

Bonding position of heterocyclic ring R⁵ R⁶ R⁷ p (R⁸) r 1 H H H 0 H 1 H H H 1 H 1 H H H 2 H 1 H H H 3 H 1 H H H 4 H 1 H H H 5 H 1 H H H 6 H 1 H H H 0 2-CH₃ 1 H H H 1 2-CH₃ 1 H H H 2 2-CH₃ 1 H H H 3 2-CH₃ 1 H H H 4 2-CH₃ 1 H H H 5 2-CH₃ 1 H H H 6 2-CH₃ 1 H H H 1 2-CH₂CH₃ 1 H H H 0 2-CH₂CH₃ 1 H H H 2 2-CH₂CH₃ 1 H H H 3 2-CH₂CH₃ 1 H H H 4 2-CH₂CH₃ 1 H H H 5 2-CH₂CH₃ 1 H H H 6 2-CH₂CH₃ 1 H H H 0 2-CH₂CH₂CH₃ 1 H H H 1 2-CH₂CH₂CH₃ 1 H H H 2 2-CH₂CH₂CH₃ 1 H H H 3 2-CH₂CH₂CH₃ 1 H H H 4 2-CH₂CH₂CH₃ 1 H H H 5 2-CH₂CH₂CH₃ 1 H H H 6 2-CH₂CH₂CH₃ 1 H H H 0 2-CH(CH₃)₂ 1 H H H 1 2-CH(CH₃)₂ 1 H H H 2 2-CH(CH₃)₂ 1 H H H 3 2-CH(CH₃)₂ 1 H H H 4 2-CH(CH₃)₂ 1 H H H 5 2-CH(CH₃)₂ 1 H H H 6 2-CH(CH₃)₂ 1 H H H 0 2-CH(CH₃)₂ 1 H H H 1 4,5-Cl₂ 1 H H H 2 4,5-Cl₂ 1 H H H 3 4,5-Cl₂ 1 H H H 4 4,5-Cl₂ 1 H H H 5 4,5-Cl₂ 1 H H H 6 4,5-Cl₂ 1 H H H 0 2,4,5-Cl₃ 1 H H H 1 2,4,5-Cl₃ 1 H H H 2 2,4,5-Cl₃ 1 H H H 3 2,4,5-Cl₃ 1 H H H 4 2,4,5-Cl₃ 1 H H H 5 2,4,5-Cl₃ 1 H H H 6 2,4,5-Cl₃ 1 H H H 0 4,5-Br₂ 1 H H H 1 4,5-Br₂ 1 H H H 2 4,5-Br₂ 1 H H H 3 4,5-Br₂ 1 H H H 4 4,5-Br₂ 1 H H H 5 4,5-Br₂ 1 H H H 6 4,5-Br₂ 1 H H H 0 2,4,5-Br₃ 1 H H H 1 2,4,5-Br₃ 1 H H H 2 2,4,5-Br₃ 1 H H H 3 2,4,5-Br₃ 1 H H H 4 2,4,5-Br₃ 1 H H H 5 2,4,5-Br₃ 1 H H H 6 2,4,5-Br₃ 1 H H H 0 4,5-(CN)₂ 1 H H H 1 4,5-(CN)₂ 1 H H H 2 4,5-(CN)₂ 1 H H H 3 4,5-(CN)₂ 1 H H H 4 4,5-(CN)₂ 1 H H H 5 4,5-(CN)₂ 1 H H H 6 4,5-(CN)₂ 1 H H CH₃ 0 H 1 H H H 0 2-NO₂ 1 H H H 1 2-NO₂ 1 H H H 2 2-NO₂ 1 H H H 3 2-NO₂ 1 H H H 4 2-NO₂ 1 H H H 5 2-NO₂ 1 H H H 6 2-NO₂ 4 H H H 0 H 4 H H H 1 H 4 H H H 2 H 5 H H H 0 4-CH₃ 2 H H H 0 H

TABLE 16

Bonding position of heterocyclic ring B R⁵ R⁶ R⁷ p (R⁸) r 2 S H H H 0 H 2 S H H H 1 H 2 S H H H 2 H 2 S H H H 3 H 2 S H H H 4 H 2 S H H H 5 H 2 S H H H 6 H 2 S H H H 0 1-CH₃ 2 S H H H 1 1-CH₃ 2 S H H H 2 1-CH₃ 2 S H H H 3 1-CH₃ 2 S H H H 4 1-CH₃ 2 S H H H 5 1-CH₃ 2 S H H H 6 1-CH₃

TABLE 17

Bonding position of heterocyclic ring R⁵ R⁶ R⁷ p (R⁸) r 4 H H H 0 3,6-Cl₂ 4 H H H 1 3,6-Cl₂ 4 H H H 2 3,6-Cl₂ 4 H H H 3 3,6-Cl₂ 4 H H H 4 3,6-Cl₂ 4 H H H 5 3,6-Cl₂ 4 H H H 6 3,6-Cl₂

TABLE 18

Bonding position of heterocyclic ring R⁵ R⁶ R⁷ p (R⁸) r 3 H H H 0 H 3 H H H 1 H 3 H H H 2 H 3 H H H 3 H 3 H H H 4 H 3 H H H 5 H 3 H H H 6 H

TABLE 19

Bonding position of heterocyclic ring R⁵ R⁶ R⁷ p (R⁸) r 1 H H H 0 H 1 H H H 1 H 1 H H H 2 H 1 H H H 3 H 1 H H H 4 H 1 H H H 5 H 1 H H H 6 H 4 H H H 0 H 4 H H H 1 H 4 H H H 2 H 4 H H H 3 H 4 H H H 4 H 4 H H H 5 H 4 H H H 6 H

TABLE 20

Bonding position of heterocyclic ring B R⁵ R⁶ R⁷ p (R⁸) r 3 S H H H 0 H 3 S H H H 1 H 3 S H H H 2 H 3 S H H H 3 H 3 S H H H 4 H 3 S H H H 5 H 3 S H H H 6 H 5 S H H H 0 1-CH₃ 5 S H H H 1 1-CH₃ 5 S H H H 2 1-CH₃ 5 S H H H 3 1-CH₃ 5 S H H H 4 1-CH₃ 5 S H H H 5 1-CH₃ 5 S H H H 6 1-CH₃

TABLE 21

Bonding position of heterocyclic ring R⁵ R⁶ R⁷ p (R⁸) r 1 H H H 0 H 1 H H H 1 H 1 H H H 2 H 1 H H H 3 H 1 H H H 4 H 1 H H H 5 H 1 H H H 6 H

TABLE 22

Bonding position of heterocyclic ring B R⁵ R⁶ R⁷ p (R⁸) r 5 S H H H 0 1-CH₃ 5 S H H H 1 1-CH₃ 5 S H H H 2 1-CH₃ 5 S H H H 3 1-CH₃ 5 S H H H 4 1-CH₃ 5 S H H H 5 1-CH₃ 5 S H H H 6 1-CH₃

TABLE 23

Bonding position of heterocyclic ring R⁵ R⁶ R⁷ p (R⁸) r 4 H H H 0 H 4 H H H 1 H 4 H H H 2 H 4 H H H 3 H 4 H H H 4 H 4 H H H 5 H 4 H H H 6 H 4 H H H 0 6-CH₃ 4 H H H 1 6-CH₃ 4 H H H 2 6-CH₃ 4 H H H 3 6-CH₃ 4 H H H 4 6-CH₃ 4 H H H 5 6-CH₃ 4 H H H 6 6-CH₃ 4 H H H 0 2,6-Cl₂

TABLE 24

Bonding position of heterocyclic ring B R⁵ R⁶ R⁷ p (R⁸) r 2 O H H H 6 4-CH₃ 4 O H H H 0 2,6-(CH₃)₂ 4 O H H H 1 2,6-(CH₃)₂ 4 O H H H 2 2,6-(CH₃)₂ 4 O H H H 3 2,6-(CH₃)₂ 4 O H H H 4 2,6-(CH₃)₂ 4 O H H H 5 2,6-(CH₃)₂ 4 O H H H 6 2,6-(CH₃)₂ 2 S H H H 0 H 2 S H H H 1 H 2 S H H H 2 H 2 S H H H 3 H 2 S H H H 4 H 2 S H H H 5 H 2 S H H H 6 H 2 NH H H H 1 H 2 NH H H H 0 H 2 O H H H 2 5-CF₃ 2 O H H H 3 5-CF₃ 5 O H H H 2 5-CF₃ 5 O H H H 3 5-CF₃ 2 NH H H H 2 H 2 NH H H H 3 H 2 NH H H H 4 H 3 NH H H H 5 H 3 NH H H H 6 H 3 S H H H 0 4-CH₃ 3 S H H H 1 4-CH₃ 3 S H H H 2 4-CH₃ 3 S H H H 3 4-CH₃ 3 S H H H 4 4-CH₃ 2 O H H H 0 H 2 O H H H 1 H 2 O H H H 2 H 2 O H H H 3 H 2 O H H H 4 H 2 O H H H 5 H 2 O H H H 6 H 2 O H H H 0 4,6-(CH₃)₂ 2 O H H H 1 4,6-(CH₃)₂ 2 O H H H 2 4,6-(CH₃)₂ 2 O H H H 3 4,6-(CH₃)₂ 2 O H H H 4 4,6-(CH₃)₂ 2 O H H H 5 4,6-(CH₃)₂ 2 O H H H 6 4,6-(CH₃)₂ 2 NH H H H 0 4,6-(CH₃)₂ 2 NH H H H 1 4,6-(CH₃)₂ 2 NH H H H 2 4,6-(CH₃)₂ 2 NH H H H 3 4,6-(CH₃)₂ 2 NH H H H 4 4,6-(CH₃)₂ 2 NH H H H 5 4,6-(CH₃)₂ 2 NH H H H 6 4,6-(CH₃)₂ 2 O H H H 0 4-CH₃ 2 O H H H 1 4-CH₃ 2 O H H H 2 4-CH₃ 2 O H H H 3 4-CH₃ 2 O H H H 4 4-CH₃ 2 S H H H 5 4-CH₃ 2 S H H H 5 4-CH₃ 2 S H H H 6 4-CH₃ 2 NH H H H 0 4-CH₃ 2 NH H H H 1 4-CH₃ 2 NH H H H 2 4-CH₃ 2 NH H H H 3 4-CH₃ 2 NH H H H 4 4-CH₃ 2 NH H H H 5 4-CH₃ 2 NH H H H 6 4-CH₃ 2 S H H H 0 4,6-(CH₃)₂ 2 S H H H 1 4,6-(CH₃)₂ 2 S H H H 2 4,6-(CH₃)₂ 2 S H H H 3 4,6-(CH₃)₂ 2 S H H H 4 4,6-(CH₃)₂ 2 S H H H 5 4,6-(CH₃)₂ 2 S H H H 0 4,6-Cl₂ 2 S H H H 6 4,6-(CH₃)₂ 2 S H H H 1 4,6-Cl₂ 2 S H H H 2 4,6-Cl₂ 2 S H H H 3 4,6-Cl₂ 2 S H H H 4 4,6-Cl₂ 2 S H H H 5 4,6-Cl₂ 2 S H H H 6 4,6-Cl₂ 4 NH H H H 0 H 4 NH H H H 1 H 4 NH H H H 2 H 4 NH H H H 3 H 4 NH H H H 4 H 4 NH H H H 5 H 4 NH H H H 6 H 2 NH H H H 0 5-Br 2 NH H H H 1 5-Br 2 NH H H H 2 5-Br 2 NH H H H 3 5-Br 2 NH H H H 4 5-Br 2 NH H H H 5 5-Br 2 NH H H H 6 5-Br 4 NH H H H 0 2,6-(CH₃)₂ 4 NH H H H 1 2,6-(CH₃)₂ 4 NH H H H 2 2,6-(CH₃)₂ 4 NH H H H 3 2,6-(CH₃)₂ 4 NH H H H 4 2,6-(CH₃)₂ 4 NH H H H 5 2,6-(CH₃)₂ 4 NH H H H 6 2,6-(CH₃)₂ 2 NH H H H 0 4-Cl, 6-CH₃ 2 NH H H H 1 4-Cl, 6-CH₃ 2 NH H H H 2 4-Cl, 6-CH₃ 2 NH H H H 3 4-Cl, 6-CH₃ 2 NH H H H 4 4-Cl, 6-CH₃ 2 NH H H H 5 4-Cl, 6-CH₃ 2 NH H H H 6 4-Cl, 6-CH₃ 2 NH H H H 0 4-OCH₃, 6-CH₃ 2 NH H H H 1 4-OCH₃, 6-CH₃ 2 NH H H H 2 4-OCH₃, 6-CH₃ 2 NH H H H 3 4-OCH₃, 6-CH₃ 2 NH H H H 4 4-OCH₃, 6-CH₃ 2 NH H H H 5 4-OCH₃, 6-CH₃ 2 NH H H H 6 4-OCH₃, 6-CH₃ 2 O H H H 0 4,6-(OCH₃)₂ 2 O H H H 1 4,6-(OCH₃)₂ 2 O H H H 2 4,6-(OCH₃)₂ 2 O H H H 3 4,6-(OCH₃)₂ 2 O H H H 4 4,6-(OCH₃)₂ 2 O H H H 5 4,6-(OCH₃)₂ 2 O H H H 6 4,6-(OCH₃)₂ 2 NH H H H 0 4,6-(OCH₃)₂ 2 NH H H H 1 4,6-(OCH₃)₂ 2 NH H H H 2 4,6-(OCH₃)₂ 2 NH H H H 4 4,6-(OCH₃)₂ 2 NH H H H 3 4,6-(OCH₃)₂ 2 NH H H H 2 5-CF₃ 2 NH H H H 3 5-CF₃ 5 NH H H H 2 5-CF₃ 5 NH H H H 3 5-CF₃ 2 NH H H H 5 4,6-(OCH₃)₂ 2 NH H H H 6 4,6-(OCH₃)₂ 2 S H H H 0 4,6-(OCH₃)₂ 2 S H H H 1 4,6-(OCH₃)₂ 2 S H H H 2 4,6-(OCH₃)₂ 2 S H H H 3 4,6-(OCH₃)₂ 2 S H H H 4 4,6-(OCH₃)₂ 2 S H H H 5 4,6-(OCH₃)₂ 2 S H H H 6 4,6-(OCH₃)₂ 5 NH H H H 0 4,6-Cl₂ 5 NH H H H 1 4,6-Cl₂ 2 S H H H 2 5-CF₃ 2 S H H H 3 5-CF₃ 5 S H H H 2 5-CF₃ 5 S H H H 3 5-CF₃

TABLE 25

Bonding position of heterocyclic ring R⁵ R⁶ R⁷ p (R⁸)_(r) 2 H H H 0 H 2 H H H 1 H 2 H H H 2 H 2 H H H 3 H 2 H H H 4 H 2 H H H 5 H 2 H H H 6 5-CH₃ 2 H H H 0 5-CH₃ 2 H H H 1 5-CH₃ 2 H H H 2 5-CH₃ 2 H H H 3 5-CH₃ 2 H H H 4 5-CH₃ 2 H H H 5 5-CH₃ 2 H H H 6 5-CH₃ 2 H H H 0 6-CH₃ 2 H H H 1 6-CH₃ 2 H H H 2 6-CH₃ 2 H H H 3 6-CH₃ 2 H H H 4 6-CH₃ 2 H H H 5 6-CH₃ 2 H H H 6 6-CH₃ 2 H H H 0 3-CH₃ 2 H H H 1 3-CH₃ 2 H H H 2 3-CH₃ 2 H H H 3 3-CH₃ 2 H H H 4 3-CH₃ 2 H H H 5 3-CH₃ 2 H H H 6 3-CH₃ 2 H H H 0 5-CH₃ 2 H H H 1 5-CH₃ 2 H H H 2 5-CH₃ 2 H H H 3 5-CH₃ 2 H H H 4 5-CH₃ 2 H H H 5 5-CH₃ 2 H H H 6 5-CH₃ 2 H H H 0 3-OCH₃ 2 H H H 1 3-OCH₃ 2 H H H 2 3-OCH₃ 2 H H H 3 3-OCH₃ 2 H H H 4 3-OCH₃ 2 H H H 5 3-OCH₃ 2 H H H 6 3-OCH₃ 2 H H H 0 6-OCH₂CH₂CH₃ 2 H H H 1 6-OCH₂CH₂CH₃ 2 H H H 2 6-OCH₂CH₂CH₃ 2 H H H 3 6-OCH₂CH₂CH₃ 2 H H H 4 6-OCH₂CH₂CH₃ 2 H H H 5 6-OCH₂CH₂CH₃ 2 H H H 6 6-OCH₂CH₂CH₃

TABLE 26

Bonding position of heterocyclic ring B R⁵ R⁶ R⁷ p (R⁸)_(r) 2 O H H H 0 H 2 O H H H 1 H 2 O H H H 2 H 2 O H H H 3 H 2 O H H H 4 H 2 O H H H 5 H 2 O H H H 6 H 2 NH H H H 0 H 2 NH H H H 1 H 2 NH H H H 2 H 2 NH H H H 3 H 2 NH H H H 4 H 2 NH H H H 5 H 2 NH H H H 6 H 2 S H H H 0 H 2 S H H H 1 H 2 S H H H 2 H 2 S H H H 3 H 2 S H H H 4 H 2 S H H H 5 H 2 S H H H 6 H 2 O H H H 0 6-Cl 2 O H H H 1 6-Cl 2 O H H H 2 6-Cl 2 O H H H 3 6-Cl 2 O H H H 4 6-Cl 2 O H H H 5 6-Cl 2 O H H H 6 6-Cl 2 NH H H H 0 6-Cl 2 NH H H H 1 6-Cl 2 NH H H H 2 6-Cl 2 NH H H H 3 6-Cl 2 NH H H H 4 6-Cl 2 NH H H H 5 6-Cl 2 NH H H H 6 6-Cl 2 S H H H 0 6-Cl 2 S H H H 1 6-Cl 2 S H H H 2 6-Cl 2 S H H H 3 6-Cl 2 S H H H 4 6-Cl 2 S H H H 5 6-Cl 2 S H H H 6 6-Cl

TABLE 27

Bonding position of heterocyclic ring B R⁵ R⁶ R⁷ p (R⁸)_(r) 3 NH H H H 0 H 3 NH H H H 1 H 3 NH H H H 2 H 3 NH H H H 3 H 3 NH H H H 4 H 3 NH H H H 5 H 3 NH H H H 6 H

TABLE 28

Bonding position of heterocyclic ring B R⁵ R⁶ R⁷ p (R⁸)_(r) 2 O H H H 0 4,6-Cl₂ 2 O H H H 1 4,6-Cl₂ 2 O H H H 2 4,6-Cl₂ 2 O H H H 3 4,6-Cl₂ 2 O H H H 4 4,6-Cl₂ 2 O H H H 5 4,6-Cl₂ 2 O H H H 6 4,6-Cl₂ 2 S H H H 0 4,6-Cl₂ 2 S H H H 1 4,6-Cl₂ 2 S H H H 2 4,6-Cl₂ 2 S H H H 3 4,6-Cl₂ 2 S H H H 4 4,6-Cl₂ 2 S H H H 5 4,6-Cl₂ 2 S H H H 6 4,6-Cl₂ 2 NH H H H 0 4,6-Cl₂ 2 NH H H H 2 4,6-Cl₂ 2 NH H H H 1 4,6-Cl₂ 2 NH H H H 3 4,6-Cl₂ 2 NH H H H 4 4,6-Cl₂ 2 NH H H H 5 4,6-Cl₂ 2 NH H H H 6 4,6-Cl₂ 2 O H H H 0 4-Cl, 6-OCH₃ 2 O H H H 1 4-Cl, 6-OCH₃ 2 O H H H 2 4-Cl, 6-OCH₃ 2 O H H H 3 4-Cl, 6-OCH₃ 2 O H H H 4 4-Cl, 6-OCH₃ 2 O H H H 5 4-Cl, 6-OCH₃ 2 O H H H 6 4-Cl, 6-OCH₃ 2 NH H H H 1 4-Cl, 6-OCH₃ 2 NH H H H 0 4-Cl, 6-OCH₃ 2 NH H H H 2 4-Cl, 6-OCH₃ 2 NH H H H 3 4-Cl, 6-OCH₃ 2 NH H H H 4 4-Cl, 6-OCH₃ 2 NH H H H 5 4-Cl, 6-OCH₃ 2 NH H H H 6 4-Cl, 6-OCH₃ 2 S H H H 0 4-Cl, 6-OCH₃ 2 S H H H 1 4-Cl, 6-OCH₃ 2 S H H H 2 4-Cl, 6-OCH₃ 2 S H H H 3 4-Cl, 6-OCH₃ 2 S H H H 4 4-Cl, 6-OCH₃ 2 S H H H 5 4-Cl, 6-OCH₃ 2 S H H H 6 4-Cl, 6-OCH₃

TABLE 29

Bonding position of heterocyclic ring R⁵ R⁶ R⁷ p (R⁸)_(r) 3 H H H 0 H 3 H H H 0 6-Cl 3 H H H 0 6-Br 3 H H H 0 6-I 3 H H H 0 6-CH₃ 3 H H H 0 6-CF₃ 3 H H CH₃ 0 H 3 H H H 0 2-CH₃ 3 H H H 0 4-(CH₂)₃CH₃ 3 H H H 0 2-Cl 3 H H H 0 4-Br 3 H H H 0 2,6-Cl₂ 3 H H H 0 2-Cl, 6-CH₃ 3 H H H 0 5,6-Cl₂ 3 H H H 0 2,6-(OCH₃)₂ 3 H H H 0 2-SCH₃ 3 H H H 0 5-CH₃ 3 H H H 1 H 3 H H H 2 H 3 H H H 3 H 3 H H H 4 H 3 H H H 5 H 3 H H H 6 H 3 H H H 1 5-CH₃ 3 H H H 2 5-CH₃ 3 H H H 3 5-CH₃ 3 H H H 4 5-CH₃ 3 H H H 5 5-CH₃ 3 H H H 6 5-CH₃ 3 H H CH₃ 1 H 3 H H CH₃ 2 H 3 H H CH₃ 4 H 3 H H CH₃ 5 H 3 H H CH₃ 3 H 3 H H CH₃ 6 H 3 H H CH₃ 1 2-CH₃ 3 H H CH₃ 2 2-CH₃ 3 H H CH₃ 3 2-CH₃ 3 H H CH₃ 4 2-CH₃ 3 H H CH₃ 5 2-CH₃ 3 H H CH₃ 6 2-CH₃ 3 H H CH₃ 1 6-CH₃ 3 H H CH₃ 2 6-CH₃ 3 H H CH₃ 3 6-CH₃ 3 H H H 4 6-CH₃ 3 H H H 6 6-CH₃ 3 H H H 5 6-CH₃ 3 H H H 1 6-Cl 3 H H H 2 6-Cl 3 H H H 3 6-Cl 3 H H H 4 6-Cl 3 H H H 5 6-Cl 3 H H H 6 6-Cl 3 H H H 1 6-Br 3 H H H 2 6-Br 3 H H H 3 6-Br 3 H H H 4 6-Br 3 H H H 5 6-Br 3 H H H 6 6-Br 3 H H H 1 6-I 3 H H H 2 6-I 3 H H H 3 6-I 3 H H H 4 6-I 3 H H H 5 6-I 3 H H H 6 6-I 3 H H H 1 6-CF₃ 3 H H H 2 6-CF₃ 3 H H H 3 6-CF₃ 3 H H H 4 6-CF₃ 3 H H H 5 6-CF₃ 3 H H H 6 6-CF₃ 3 H H H 1 2-Cl 3 H H H 2 2-Cl 3 H H H 3 2-Cl 3 H H H 4 2-Cl 3 H H H 5 2-Cl 3 H H H 6 2-Cl 3 H H H 1 5-Br 3 H H H 2 5-Br 3 H H H 3 5-Br 3 H H H 4 5-Br 3 H H H 5 5-Br 3 H H H 6 5-Br 3 H H H 1 2-Cl, 6-CH₃ 3 H H H 2 2-Cl, 6-CH₃ 3 H H H 4 2-Cl, 6-CH₃ 3 H H H 3 2-Cl, 6-CH₃ 3 H H H 5 2-Cl, 6-CH₃ 3 H H H 6 2-Cl, 6-CH₃ 3 H H H 1 2,6-Cl₂ 3 H H H 2 2,6-Cl₂ 3 H H H 3 2,6-Cl₂ 3 H H H 4 2,6-Cl₂ 3 H H H 5 2,6-Cl₂ 3 H H H 6 2,6-Cl₂ 3 H H H 1 5,6-Cl₂ 3 H H H 2 5,6-Cl₂ 3 H H H 3 5,6-Cl₂ 3 H H H 4 5,6-Cl₂ 3 H H H 5 5,6-Cl₂ 3 H H H 6 5,6-Cl₂ 3 H H H 1 5,6-(OCH₃)₂ 3 H H H 2 5,6-(OCH₃)₂ 3 H H H 3 5,6-(OCH₃)₂ 3 H H H 4 5,6-(OCH₃)₂ 3 H H H 5 5,6-(OCH₃)₂ 3 H H H 6 5,6-(OCH₃)₂ 3 H H H 1 2-SCH₃ 3 H H H 2 2-SCH₃ 3 H H H 3 2-SCH₃ 3 H H H 4 2-SCH₃ 3 H H H 5 2-SCH₃ 3 H H H 6 2-SCH₃ 2 H H H 0 H 2 H H H 1 H 2 H H H 2 H 2 H H H 3 H 2 H H H 4 H 2 H H H 5 H 2 H H H 6 H 2 H H H 0 6-CH₃ 2 H H H 1 6-CH₃ 2 H H H 2 6-CH₃ 2 H H H 3 6-CH₃ 2 H H H 4 6-CH₃ 2 H H H 5 6-CH₃ 2 H H H 6 6-CH₃ 2 H H H 0 6-Cl 2 H H H 1 6-Cl 2 H H H 2 6-Cl 2 H H H 3 6-Cl 2 H H H 4 6-Cl 2 H H H 5 6-Cl 2 H H H 6 6-Cl 2 H H H 0 5-CF₃ 2 H H H 1 5-CF₃ 2 H H H 2 5-CF₃ 2 H H H 3 5-CF₃ 2 H H H 4 5-CF₃ 2 H H H 5 5-CF₃ 2 H H H 0 5-Cl 2 H H H 6 5-CF₃ 2 H H H 1 5-Cl 2 H H H 2 5-Cl 2 H H H 3 5-Cl 2 H H H 4 5-Cl 2 H H H 5 5-Cl 2 H H H 6 5-Cl 2 H H H 0 3-Cl 2 H H H 1 3-Cl 2 H H H 2 3-Cl 2 H H H 3 3-Cl 2 H H H 4 3-Cl 2 H H H 5 3-Cl 2 H H H 6 3-Cl 2 H H H 0 6-F 2 H H H 1 6-F 2 H H H 2 6-F 2 H H H 3 6-F 2 H H H 4 6-F 2 H H H 5 6-F 2 H H H 6 6-F 2 H H H 0 6-Br 2 H H H 1 6-Br 2 H H H 2 6-Br 2 H H H 3 6-Br 2 H H H 4 6-Br 2 H H H 5 6-Br 2 H H H 6 6-Br 3 H H H 0 6-Cl 3 H H H 1 6-Cl 3 H H H 2 6-Cl 3 H H H 3 6-Cl 3 H H H 4 6-Cl 3 H H H 5 6-Cl 3 H H H 6 6-Cl 3 H H H 0 5-Cl 3 H H H 1 5-Cl 3 H H H 2 5-Cl 2 H H H 3 5-Cl 2 H H H 4 5-Cl 2 H H H 5 5-Cl 2 H H H 6 5-Cl 2 H H H 0 5-Br 2 H H H 1 5-Br 2 H H H 2 5-Br 2 H H H 3 5-Br 2 H H H 4 5-Br 2 H H H 5 5-Br 2 H H H 6 5-Br 2 H H H 0 3,5-(CF₃)₂ 2 H H H 1 3,5-(CF₃)₂ 2 H H H 2 3,5-(CF₃)₂ 2 H H H 3 3,5-(CF₃)₂ 2 H H H 4 3,5-(CF₃)₂ 2 H H H 5 3,5-(CF₃)₂ 2 H H H 6 3,5-(CF₃)₂ 2 H H H 0 4,5-(CF₃)₂ 2 H H H 1 4,5-(CF₃)₂ 2 H H H 2 4,5-(CF₃)₂ 2 H H H 3 4,5-(CF₃)₂ 2 H H H 4 4,5-(CF₃)₂ 2 H H H 5 4,5-(CF₃)₂ 2 H H H 6 4,5-(CF₃)₂ 2 H H H 0 3,5-Cl₂ 2 H H H 1 3,5-Cl₂ 2 H H H 2 3,5-Cl₂ 2 H H H 3 3,5-Cl₂ 2 H H H 4 3,5-Cl₂ 2 H H H 5 3,5-Cl₂ 2 H H H 6 3,5-Cl₂ 2 H H H 0 3-Cl, 5-CF₃ 2 H H H 1 3-Cl, 5-CF₃ 2 H H H 2 3-Cl, 5-CF₃ 2 H H H. 3 3-Cl, 5-CF₃ 2 H H H 4 3-Cl, 5-CF₃ 2 H H H 5 3-Cl, 5-CF₃ 2 H H H 6 3-Cl, 5-CF₃ 2 H H H 0 3,5,6-F₃ 2 H H H 0 3,5,6-F₃, 4CH₃ 2 H H H 0 5-CN, 6-Cl 4 H H H 0 H 4 H H H 1 H 4 H H H 2 H 4 H H H 3 H 4 H H H 4 H 4 H H H 5 H 4 H H H 6 H 4 H H H 0 2,3,5,6-F₄ 4 H H CH₃ 0 H 4 H H CH₃ 1 H 4 H H CH₃ 2 H 4 H H CH₃ 3 H 4 H H CH₃ 4 H 4 H H CH₃ 5 H 4 H H CH₃ 6 H 2 H H CH₃ 0 H 2 H H CH₃ 1 H 2 H H CH₃ 2 H 2 H H CH₃ 3 H 2 H H CH₃ 4 H 2 H H CH₃ 5 H 2 H H CH₃ 6 H

TABLE 30

Bonding position of heterocyclic ring B R⁵ R⁶ R⁷ p (R⁸)_(r) 2 O H H H 0 H 2 O H H H 1 H 2 O H H H 2 H 2 O H H H 3 H 2 O H H H 4 H 2 O H H H 5 H 2 O H H H 6 H 2 NH H H H 0 H 2 NH H H H 1 H 2 NH H H H 2 H 2 NH H H H 3 H 2 NH H H H 4 H 2 NH H H H 5 H 2 NH H H H 6 H 2 S H H H 0 H 2 S H H H 1 H 2 S H H H 2 H 2 S H H H 3 H 2 S H H H 4 H 2 S H H H 5 H 2 S H H H 6 H 2 O H H H 0 4-CH₃ 2 O H H H 1 4-CH₃ 2 O H H H 2 4-CH₃ 2 O H H H 3 4-CH₃ 2 O H H H 4 4-CH₃ 2 O H H H 5 4-CH₃ 2 O H H H 6 4-CH₃ 2 NH H H H 0 4-CH₃ 2 NH H H H 1 4-CH₃ 2 NH H H H 2 4-CH₃ 2 NH H H H 3 4-CH₃ 2 NH H H H 4 4-CH₃ 2 NH H H H 5 4-CH₃ 2 NH H H H 6 4-CH₃ 2 S H H H 0 4-CH₃ 2 S H H H 1 4-CH₃ 2 S H H H 2 4-CH₃ 2 S H H H 3 4-CH₃ 2 S H H H 4 4-CH₃ 2 S H H H 5 4-CH₃ 2 S H H H 6 4-CH₃ 2 O H H H 0 6-CH₃ 2 O H H H 1 6-CH₃ 2 O H H H 2 6-CH₃ 2 O H H H 3 6-CH₃ 2 O H H H 4 6-CH₃ 2 O H H H 5 6-CH₃ 2 O H H H 6 6-CH₃ 2 NH H H H 0 6-CH₃ 2 NH H H H 1 6-CH₃ 2 NH H H H 2 6-CH₃ 2 NH H H H 3 6-CH₃ 2 NH H H H 4 6-CH₃ 2 COO H H H 1 H 2 COO H H H 2 H 2 COO H H H 3 H 3 COO H H H 1 H 3 COO H H H 2 H 3 COO H H H 3 H 4 COO H H H 1 H 4 COO H H H 2 H 4 COO H H H 3 H 2 COO H H H 2 3-Cl, 5-CF₃ 2 COO H H H 3 3-Cl, 5-CF₃ 2 COO H H H 2 5-CF₃ 2 COO H H H 3 5-CF₃ 3 COO H H H 2 6-CF₃ 3 COO H H H 3 6-CF₃ 3 COO H H H 2 6-CH₃ 3 COO H H H 3 6-CH₃ 3 COO H H H 2 6-Cl 3 COO H H H 3 6-Cl 3 COO H H H 2 6-Br 3 COO H H H 3 6-Br 3 COO H H H 2 6-I 3 COO H H H 3 6-I 2 NH H H H 5 6-CH₃ 2 NH H H H 6 6-CH₃ 2 S H H H 0 6-CH₃ 2 S H H H 1 6-CH₃ 2 S H H H 2 6-CH₃ 2 S H H H 3 6-CH₃ 2 S H H H 4 6-CH₃ 2 S H H H 5 6-CH₃ 2 S H H H 6 6-CH₃ 2 O H H H 0 6-Cl 2 O H H H 1 6-Cl 2 O H H H 2 6-Cl 2 O H H H 3 6-Cl 2 O H H H 4 6-Cl 2 O H H H 5 6-Cl 2 O H H H 6 6-Cl 2 S H H H 0 6-Cl 2 S H H H 1 6-Cl 2 S H H H 2 6-Cl 2 S H H H 3 6-Cl 2 S H H H 4 6-Cl 2 S H H H 5 6-Cl 2 S H H H 6 6-Cl 2 NH H H H 0 6-Cl 2 NH H H H 1 6-Cl 2 NH H H H 2 6-Cl 2 NH H H H 3 6-Cl 2 NH H H H 4 6-Cl 2 NH H H H 5 6-Cl 2 NH H H H 6 6-Cl 2 O H H H 0 5-Cl 2 O H H H 1 5-Cl 2 O H H H 2 5-Cl 2 O H H H 3 5-Cl 2 O H H H 4 5-Cl 2 O H H H 5 5-Cl 2 O H H H 6 5-Cl 2 NH H H H 0 5-Cl 2 NH H H H 1 5-Cl 2 NH H H H 2 5-Cl 2 NH H H H 3 5-Cl 2 NH H H H 4 5-Cl 2 NH H H H 5 5-Cl 2 NH H H H 6 5-Cl 2 S H H H 0 5-Cl 2 S H H H 1 5-Cl 2 S H H H 2 5-Cl 2 S H H H 3 5-Cl 2 S H H H 4 5-Cl 2 S H H H 5 5-Cl 2 S H H H 6 5-Cl 2 N-CH₃ H H H 0 5-Cl 2 N-CH₃ H H H 1 5-Cl 2 N-CH₃ H H H 2 5-Cl 2 N-CH₃ H H H 3 H 2 N-CH₃ H H H 4 H 2 N-CH₃ H H H 5 H 2 N-CH₃ H H H 6 H 2 NH H H H 0 3-CH₃ 2 NH H H H 1 3-CH₃ 2 NH H H H 2 3-CH₃ 2 NH H H H 3 3-CH₃ 2 NH H H H 4 3-CH₃ 2 NH H H H 5 3-CH₃ 2 NH H H H 6 3-CH₃ 2 S H H H 0 3-CH₃ 2 S H H H 1 3-CH₃ 2 S H H H 2 3-CH₃ 2 S H H H 3 3-CH₃ 2 S H H H 4 3-CH₃ 2 S H H H 5 3-CH₃ 2 S H H H 6 3-CH₃ 2 O H H H 0 3-CH₃ 2 O H H H 1 3-CH₃ 2 O H H H 2 3-CH₃ 2 O H H H 3 3-CH₃ 2 O H H H 4 3-CH₃ 2 O H H H 5 3-CH₃ 2 O H H H 6 3-CH₃ 2 NH H H H 0 5-CH₃ 2 NH H H H 1 5-CH₃ 2 NH H H H 2 5-CH₃ 2 NH H H H 3 5-CH₃ 2 NH H H H 4 5-CH₃ 2 NH H H H 5 5-CH₃ 2 NH H H H 6 5-CH₃ 2 O H H H 0 5-CH₃ 2 O H H H 1 5-CH₃ 2 O H H H 2 5-CH₃ 2 O H H H 3 5-CH₃ 2 O H H H 4 5-CH₃ 2 O H H H 5 5-CH₃ 2 O H H H 6 5-CH₃ 2 S H H H 0 5-CH₃ 2 S H H H 1 5-CH₃ 2 S H H H 2 5-CH₃ 2 S H H H 3 5-CH₃ 2 S H H H 4 5-CH₃ 2 S H H H 5 5-CH₃ 2 S H H H 6 5-CH₃ 2 NH H H H 0 5-Br 2 NH H H H 1 5-Br 2 NH H H H 2 5-Br 2 NH H H H 3 5-Br 2 NH H H H 4 5-Br 2 NH H H H 5 5-Br 2 NH H H H 6 5-Br 2 O H H H 0 5-Br 2 O H H H 1 5-Br 2 O H H H 2 5-Br 2 O H H H 3 5-Br 2 O H H H 4 5-Br 2 O H H H 5 5-Br 2 O H H H 6 5-Br 2 S H H H 0 5-Br 2 S H H H 1 5-Br 2 S H H H 2 5-Br 2 S H H H 3 5-Br 2 S H H H 4 5-Br 2 S H H H 5 5-Br 2 S H H H 6 5-Br 2 S H H H 0 5-Br 2 S H H H 1 5-Br 2 S H H H 2 5-Br 2 S H H H 3 5-Br 2 S H H H 4 5-Br 2 S H H H 5 5-Br 2 S H H H 6 5-Br 2 NH H H H 0 4,6-(CH₃)₂ 2 NH H H H 1 4,6-(CH₃)₂ 2 NH H H H 2 4,6-(CH₃)₂ 2 NH H H H 3 4,6-(CH₃)₂ 2 NH H H H 4 4,6-(CH₃)₂ 2 NH H H H 5 4,6-(CH₃)₂ 2 NH H H H 6 4,6-(CH₃)₂ 2 O H H H 0 4,6-(CH₃)₂ 2 O H H H 1 4,6-(CH₃)₂ 2 O H H H 2 4,6-(CH₃)₂ 2 O H H H 3 4,6-(CH₃)₂ 2 O H H H 4 4,6-(CH₃)₂ 2 O H H H 5 4,6-(CH₃)₂ 2 O H H H 6 4,6-(CH₃)₂ 2 S H H H 0 4,6-(CH₃)₂ 2 S H H H 1 4,6-(CH₃)₂ 2 S H H H 2 4,6-(CH₃)₂ 2 S H H H 3 4,6-(CH₃)₂ 2 S H H H 4 4,6-(CH₃)₂ 2 S H H H 5 4,6-(CH₃)₂ 2 S H H H 6 4,6-(CH₃)₂ 2 NH H H H 0 3-Cl, 5-CF₃ 2 NH H H H 1 3-Cl, 5-CF₃ 2 NH H H H 2 3-Cl, 5-CF₃ 2 NH H H H 3 3-Cl, 5-CF₃ 2 NH H H H 4 3-Cl, 5-CF₃ 2 NH H H H 5 3-Cl, 5-CF₃ 2 NH H H H 6 3-Cl, 5-CF₃ 2 O H H H 0 3-Cl, 5-CF₃ 2 O H H H 1 3-Cl, 5-CF₃ 2 O H H H 2 3-Cl, 5-CF₃ 2 O H H H 3 3-Cl, 5-CF₃ 2 O H H H 4 3-Cl, 5-CF₃ 2 O H H H 5 3-Cl, 5-CF₃ 2 O H H H 6 3-Cl, 5-CF₃ 2 S H H H 0 3-Cl, 5-CF₃ 2 S H H H l 3-Cl, 5-CF₃ 2 S H H H 2 3-Cl, 5-CF₃ 2 S H H H 3 3-Cl, 5-CF₃ 2 S H H H 4 3-Cl, 5-CF₃ 2 S H H H 5 3-Cl, 5-CF₃ 2 S H H H 6 3-Cl, 5-CF₃ 2 NH H H H 0 5-NO₂ 2 NH H H H 1 5-NO₂ 2 NH H H H 0 3-Br, 5-CF₃ 2 NH H H H 1 3-Br, 5-CF₃ 2 NH H H H 2 3-Br, 5-CF₃ 2 NH H H H 3 3-Br, 5-CF₃ 2 NH H H H 4 3-Br, 5-CF₃ 2 NH H H H 5 3-Br, 5-CF₃ 2 NH H H H 6 3-Br, 5-CF₃ 2 O H H H 0 3-Br, 5-CF₃ 2 O H H H l 3-Br, 5-CF₃ 2 O H H H 2 3-Br, 5-CF₃ 2 O H H H 3 3-Br, 5-CF₃ 2 O H H H 4 3-Br, 5-CF₃ 2 O H H H 5 3-Br, 5-CF₃ 2 O H H H 6 3-Br, 5-CF₃ 2 S H H H 0 3-Br, 5-CF₃ 2 S H H H 1 3-Br, 5-CF₃ 2 S H H H 2 3-Br, 5-CF₃ 2 S H H H 3 3-Br, 5-CF₃ 2 S H H H 4 3-Br, 5-CF₃ 2 S H H H 5 3-Br, 5-CF₃ 2 S H H H 6 3-Br, 5-CF₃ 2 NH H H H 0 3-F, 5-CF₃ 2 NH H H H 1 3-F, 5-CF₃ 2 NH H H H 2 3-F, 5-CF₃ 2 NH H H H 3 3-F, 5-CF₃ 2 NH H H H 4 3-F, 5-CF₃ 2 NH H H H 5 3-F, 5-CF₃ 2 NH H H H 6 3-F, 5-CF₃ 2 O H H H 0 3-F, 5-CF₃ 2 O H H H 1 3-F, 5-CF₃ 2 O H H H 2 3-F, 5-CF₃ 2 O H H H 3 3-F, 5-CF₃ 2 O H H H 4 3-F, 5-CF₃ 2 O H H H 5 3-F, 5-CF₃ 2 O H H H 6 3-F, 5-CF₃ 2 S H H H 0 3-F, 5-CF₃ 2 S H H H 1 3-F, 5-CF₃ 2 S H H H 2 3-F, 5-CF₃ 2 S H H H 3 3-F, 5-CF₃ 2 S H H H 4 3-F, 5-CF₃ 2 S H H H 5 3-F, 5-CF₃ 2 S H H H 6 3-F, 5-CF₃ 2 NH H H H 2 5-NO₂ 2 NH H H H 3 5-NO₂ 2 NH H H H 4 5-NO₂ 2 NH H H H 5 5-NO₂ 2 NH H H H 6 5-NO₂ 2 O H H H 0 5-NO₂ 2 O H H H 1 5-NO₂ 2 O H H H 2 5-NO₂ 2 O H H H 3 5-NO₂ 2 O H H H 4 5-NO₂ 2 O H H H 5 5-NO₂ 2 O H H H 6 5-NO₂ 2 S H H H 0 5-NO₂ 2 S H H H 1 5-NO₂ 2 S H H H 2 5-NO₂ 2 S H H H 3 5-NO₂ 2 S H H H 4 5-NO₂ 2 S H H H 5 5-NO₂ 2 S H H H 6 5-NO₂ 2 NH H H H 0 3-NO₂, 5-Br 2 NH H H H 1 3-NO₂, 5-Br 2 NH H H H 2 3-NO₂, 5-Br 2 NH H H H 3 3-NO₂, 5-Br 2 NH H H H 4 3-NO₂, 5-Br 2 NH H H H 5 3-NO₂, 5-Br 2 NH H H H 6 3-NO₂, 5-Br 2 O H H H 0 3-NO₂, 5-Br 2 O H H H 1 3-NO₂, 5-Br 2 O H H H 2 3-NO₂, 5-Br 2 O H H H 3 3-NO₂, 5-Br 2 O H H H 4 3-NO₂, 5-Br 2 O H H H 5 3-NO₂, 5-Br 2 O H H H 6 3-NO₂, 5-Br 2 S H H H 0 3-NO₂, 5-Br 2 S H H H 1 3-NO₂, 5-Br 2 S H H H 2 3-NO₂, 5-Br 2 S H H H 3 3-NO₂, 5-Br 2 S H H H 4 3-NO₂, 5-Br 2 S H H H 5 3-NO₂, 5-Br 2 S H H H 6 3-NO₂, 5-Br 2 NH H H H 0 3-NO₂, 4-CH₃ 2 NH H H H 1 3-NO₂, 4-CH₃ 2 NH H H H 2 3-NO₂, 4-CH₃ 2 NH H H H 3 3-NO₂, 4-CH₃ 2 NH H H H 4 3-NO₂, 4-CH₃ 2 NH H H H 5 3-NO₂, 4-CH₃ 2 NH H H H 6 3-NO₂, 4-CH₃ 2 S H H H 0 3-NO₂, 4-CH₃ 2 S H H H 1 3-NO₂, 4-CH₃ 2 S H H H 2 3-NO₂, 4-CH₃ 2 S H H H 3 3-NO₂, 4-CH₃ 2 S H H H 4 3-NO₂, 4-CH₃ 2 S H H H 5 3-NO₂, 4-CH₃ 2 S H H H 6 3-NO₂, 4-CH₃ 2 O H H H 0 3-NO₂, 4-CH₃ 2 O H H H 1 3-NO₂, 4-CH₃ 2 O H H H 2 3-NO₂, 4-CH₃ 2 O H H H 3 3-NO₂, 4-CH₃ 2 O H H H 4 3-NO₂, 4-CH₃ 2 O H H H 5 3-NO₂, 4-CH₃ 2 O H H H 6 3-NO₂, 4-CH₃ 2 NH H H H 0 4-CH₃, 5-NO₂ 2 NH H H H 1 4-CH₃, 5-NO₂ 2 NH H H H 2 4-CH₃, 5-NO₂ 2 NH H H H 3 4-CH₃, 5-NO₂ 2 NH H H H 4 4-CH₃, 5-NO₂ 2 NH H H H 5 4-CH₃, 5-NO₂ 2 NH H H H 6 4-CH₃, 5-NO₂ 2 O H H H 0 4-CH₃, 5-NO₂ 2 O H H H 1 4-CH₃, 5-NO₂ 2 O H H H 2 4-CH₃, 5-NO₂ 2 O H H H 0 3,5-(CF₃)₂ 2 O H H H 1 3,5-(CF₃)₂ 2 O H H H 2 3,5-(CF₃)₂ 2 O H H H 3 3,5-(CF₃)₂ 2 O H H H 4 3,5-(CF₃)₂ 2 O H H H 5 3,5-(CF₃)₂ 2 O H H H 6 3,5-(CF₃)₂ 2 NH H H H 0 3,5-(CF₃)₂ 2 NH H H H 1 3,5-(CF₃)₂ 2 NH H H H 2 3,5-(CF₃)₂ 2 NH H H H 3 3,5-(CF₃)₂ 2 NH H H H 4 3,5-(CF₃)₂ 2 NH H H H 5 3,5-(CF₃)₂ 2 NH H H H 6 3,5-(CF₃)₂ 2 S H H H 0 3,5-(CF₃)₂ 2 S H H H 1 3,5-(CF₃)₂ 2 S H H H 2 3,5-(CF₃)₂ 2 S H H H 3 3,5-(CF₃)₂ 2 S H H H 4 3,5-(CF₃)₂ 2 S H H H 5 3,5-(CF₃)₂ 2 S H H H 6 3,5-(CF₃)₂ 2 O H H H 0 5-CF₃ 2 O H H H 1 5-CF₃ 2 O H H H 2 5-CF₃ 2 O H H H 3 5-CF₃ 2 O H H H 4 5-CF₃ 2 O H H H 5 5-CF₃ 2 O H H H 6 5-CF₃ 2 S H H H 0 5-CF₃ 2 S H H H 1 5-CF₃ 2 S H H H 2 5-CF₃ 2 S H H H 3 5-CF₃ 2 S H H H 4 5-CF₃ 2 S H H H 5 5-CF₃ 2 S H H H 6 5-CF₃ 2 NH H H H 0 5-CF₃ 2 NH H H H 1 5-CF₃ 2 NH H H H 2 5-CF₃ 2 NH H H H 3 5-CF₃ 2 NH H H H 4 5-CF₃ 2 NH H H H 5 5-CF₃ 2 NH H H H 6 5-CF₃ 2 NCH₃ H H H 0 5-CF₃ 2 NCH₃ H H H 1 5-CF₃ 2 NCH₃ H H H 2 5-CF₃ 2 NCH₃ H H H 3 5-CF₃ 2 NCH₃ H H H 4 5-CF₃ 2 N-CH₂CH₃ H H H 0 5-CF₃ 2 N-CH₂CH₃ H H H 1 5-CF₃ 2 N-CH₂CH₃ H H H 2 5-CF₃ 2 N-CH₂CH₃ H H H 3 5-CF₃ 2 N-CH₂CH₃ H H H 4 5-CF₃ 2 N-(CH₂)₂CH₃ H H H 0 5-CF₃ 2 N-(CH₂)₂CH₃ H H H 1 5-CF₃ 2 N-(CH₂)₂CH₃ H H H 2 5-CF₃ 2 N-(CH₂)₂CH₃ H H H 3 5-CF₃ 2 N-(CH₂)₂CH₃ H H H 4 5-CF₃ 2 N-CH(CH₃)₂ H H H 0 5-CF₃ 2 N-CH(CH₃)₂ H H H 1 5-CF₃ 2 N-CH(CH₃)₂ H H H 2 5-CF₃ 2 N-CH(CH₃)₂ H H H 3 5-CF₃ 2 N-CH(CH₃)₂ H H H 4 5-CF₃ 2 O H H H 3 4-CH₃, 5-NO₂ 2 O H H H 4 4-CH₃, 5-NO₂ 2 O H H H 5 4-CH₃, 5-NO₂ 2 O H H H 6 4-CH₃, 5-NO₂ 2 S H H H 0 4-CH₃, 5-NO₂ 2 S H H H 1 4-CH₃, 5-NO₂ 2 S H H H 2 4-CH₃, 5-NO₂ 2 S H H H 3 4-CH₃, 5-NO₂ 2 S H H H 4 4-CH₃, 5-NO₂ 2 S H H H 5 4-CH₃, 5-NO₂ 2 S H H H 6 4-CH₃, 5-NO₂ 3 O H H H 0 H 3 O H H H 1 H 3 O H H H 2 H 3 O H H H 3 H 3 O H H H 4 H 3 O H H H 5 H 3 O H H H 6 H 3 O H H H 0 2-CH₃ 3 O H H H 1 2-CH₃ 3 O H H H 2 2-CH₃ 3 O H H H 3 2-CH₃ 3 O H H H 4 2-CH₃ 3 O H H H 5 2-CH₃ 3 O H H H 6 2-CH₃ 3 O H H H 0 6-CH₃ 3 O H H H 1 6-CH₃ 3 O H H H 2 6-CH₃ 3 O H H H 3 6-CH₃ 3 O H H H 4 6-CH₃ 3 O H H H 5 6-CH₃ 3 O H H H 6 6-CH₃ 3 O H H H 0 5-Cl 3 O H H H 1 5-Cl 3 O H H H 2 5-Cl 3 O H H H 3 5-Cl 3 O H H H 4 5-Cl 3 O H H H 5 5-Cl 3 O H H H 6 5-Cl 3 O H H H 0 2-Cl 3 O H H H 1 2-Cl 3 O H H H 2 2-Cl 3 O H H H 3 2-Cl 3 O H H H 4 2-Cl 3 O H H H 5 2-Cl 3 O H H H 6 2-Cl 3 O H H H 0 2-Br 3 O H H H 1 2-Br 3 O H H H 2 2-Br 3 O H H H 3 2-Br 3 O H H H 4 2-Br 3 O H H H 5 2-Br 3 O H H H 6 2-Br 3 O H H H 0 2-I, 6-CH₃ 3 O H H H 1 2-I, 6-CH₃ 3 O H H H 2 2-I, 6-CH₃ 3 O H H H 3 2-I, 6-CH₃ 3 O H H H 4 2-I, 6-CH₃ 3 O H H H 5 2-I, 6-CH₃ 3 O H H H 6 2-I, 6-CH₃ 3 NH H H H 0 H 3 NH H H H 1 H 3 NH H H H 2 H 3 NH H H H 3 H 3 NH H H H 4 H 3 NH H H H 5 H 3 NH H H H 6 H 3 NH H H H 0 2-Cl 3 NH H H H 1 2-Cl 3 NH H H H 2 2-Cl 3 NH H H H 3 2-Cl 3 NH H H H 4 2-Cl 3 NH H H H 5 2-Cl 3 NH H H H 6 2-Cl 3 NH H H H 0 5-OCH₃ 3 NH H H H 1 5-OCH₃ 3 NH H H H 2 5-OCH₃ 3 NH H H H 3 5-OCH₃ 3 NH H H H 4 5-OCH₃ 3 NH H H H 5 5-OCH₃ 3 NH H H H 6 5-OCH₃ 3 NH H H H 0 2,6-(OCH₃)₂ 3 NH H H H 1 2,6-(OCH₃)₂ 3 NH H H H 2 2,6-(OCH₃)₂ 3 NH H H H 3 2,6-(OCH₃)₂ 3 NH H H H 4 2,6-(OCH₃)₂ 3 NH H H H 5 2,6-(OCH₃)₂ 3 NH H H H 6 2,6-(OCH₃)₂ 4 S H H H 0 H 4 S H H H 1 H 4 S H H H 2 H 4 S H H H 3 H 4 S H H H 4 H 4 S H H H 5 H 4 S H H H 6 H 4 NH H H H 0 H 4 NH H H H 1 H 4 NH H H H 2 H 4 NH H H H 3 H 4 NH H H H 4 H 4 NH H H H 5 H 4 NH H H H 6 H 4 O H H H 0 H 4 O H H H 1 H 4 O H H H 2 H 4 O H H H 3 H 4 O H H H 4 H 4 O H H H 5 H 4 O H H H 6 H 4 S H H H 0 2,3,5,6-Cl₄ 4 S H H H 1 2,3,5,6-Cl₄ 4 S H H H 2 2,3,5,6-Cl₄ 4 S H H H 3 2,3,5,6-Cl₄ 4 S H H H 4 2,3,5,6-Cl₄ 4 S H H H 5 2,3,5,6-Cl₄ 4 S H H H 6 2,3,5,6-Cl₄

TABLE 31 R¹ =

TABLE 32 R¹ =

TABLE 33 R¹ =

TABLE 34 R¹ =

In Tables 31 to 34, (R⁸)_(r) is defined as followed:

(R⁸)_(r) 3-Cl, 5-CF₃ 3-Br, 5-CF₃ 3-F, 5-CF₃ 3,5-(CF₃)₂ 5-CF₃ 3,5-Cl₂ 6-Cl 6-CF₃ 6-Br

TABLE 35

(R⁸)_(r) R¹³ R¹⁴ R⁵ R⁶ p R⁷ H H H H H 0 H H H H H H 1 H 6-Cl H H H H 0 H 6-Cl H H H H 1 H 6-Br H H H H 0 H 6-Br H H H H 1 H 6-F H H H H 0 H 6-F H H H H 1 H 6-I H H H H 0 H 6-I H H H H 1 H 6-CH₃ H H H H 0 H 6-CH₃ H H H H 1 H 6-CF₃ H H H H 0 H 6-CF₃ H H H H 1 H 6-Cl CH₃ H H H 0 H 6-Cl CH₃ H H H 1 H 6-CH₃ CH₃ CH₃ H H 0 H 6-CH₃ CH₃ CH₃ H H 1 H 6-CF₃ CH₃ CH₃ H H 0 H 6-CF₃ CH₃ CH₃ H H 1 H 6-Cl CH₃ CH₃ H H 0 H 6-Cl CH₃ CH₃ H H 1 H 6-CH₃ CH₃ CH₃ H H 0 H 6-CH₃ CH₃ CH₃ H H 1 H 6-CF₃ CH₃ CH₃ H H 0 H 6-CF₃ CH₃ CH₃ H H 1 H

TABLE 36

(R⁸)_(r) R¹³ R¹⁴ R⁵ R⁶ p R⁷ H H H H H 0 H H H H H H 1 H 5-Cl H H H H 0 H 5-Cl H H H H 1 H 5-Br H H H H 0 H 5-Br H H H H 1 H 5-F H H H H 0 H 5-F H H H H 1 H 5-I H H H H 0 H 5-I H H H H 1 H 5-CH₃ H H H H 0 H 5-CH₃ H H H H 1 H 5-CF₃ H H H H 0 H 5-CF₃ H H H H 1 H 5-Cl CH₃ H H H 0 H 5-Cl CH₃ H H H 1 H 5-CH₃ CH₃ CH₃ H H 0 H 5-CH₃ CH₃ CH₃ H H 1 H 5-CF₃ CH₃ CH₃ H H 0 H 5-CF₃ CH₃ CH₃ H H 1 H 5-Cl CH₃ CH₃ H H 0 H 5-Cl CH₃ CH₃ H H 1 H 5-CH₃ CH₃ CH₃ H H 0 H 5-CH₃ CH₃ CH₃ H H 1 H 5-CF₃ CH₃ CH₃ H H 0 H 5-CF₃ CH₃ CH₃ H H 1 H

TABLE 37

(R⁸)_(r) R¹¹ R¹² s R⁵ R⁶ p R⁷ H H H 1 H H 1 H H H H 2 H H 1 H 5-Cl H H 1 H H 1 H 5-Cl H H 2 H H 1 H 5-CF₃ H H 1 H H 1 H 5-CF₃ H H 2 H H 1 H

TABLE 38

(R⁸)_(r) R¹³ R¹⁴ R⁵ R⁶ p R⁷ H H H H H 1 H H H H H H 2 H 6-Cl H H H H 1 H 6-Cl H H H H 2 H 6-Br H H H H 1 H 6-Br H H H H 2 H 6-F H H H H 1 H 6-F H H H H 2 H 6-I H H H H 1 H 6-I H H H H 2 H 6-CH₃ H H H H 1 H 6-CH₃ H H H H 2 H 6-CF₃ H H H H 1 H 6-CF₃ H H H H 2 H

TABLE 39

(R⁸)_(r) R¹³ R¹⁴ R⁵ R⁶ p R⁷ H H H H H 1 H H H H H H 2 H 5-Cl H H H H 1 H 5-Cl H H H H 2 H 5-Br H H H H 1 H 5-Br H H H H 2 H 5-F H H H H 1 H 5-F H H H H 2 H 5-I H H H H 1 H 5-I H H H H 2 H 5-CH₃ H H H H 1 H 5-CH₃ H H H H 2 H 5-CF₃ H H H H 1 H 5-CF₃ H H H H 2 H

TABLE 40

(R⁸)_(r) R¹¹ R¹² s B R⁵ R⁶ p R⁷ H H H 1 COO H H 1 H H H H 2 COO H H 1 H H H H 1 COO H H 2 H H H H 2 COO H H 2 H 6-CH₃ H H 1 COO H H 1 H 6-CH₃ H H 2 COO H H 1 H 6-CH₃ H H 1 COO H H 2 H 6-CH₃ H H 2 COO H H 2 H

TABLE 41

Bonding position of heterocyclic ring B (R₈)_(r) R⁵ R⁶ p R⁷ 2 COO H H H 2 H 2 COO H H H 3 H 3 COO H H H 2 H 3 COO H H H 3 H 2 O H H H 1 H 2 O H H H 2 H 2 O H H H 3 H 2 S H H H 1 H 2 S H H H 2 H 2 S H H H 3 H 2 NH H H H 1 H 2 NH H H H 2 H 2 NH H H H 3 H 2 NH H H H 1 H 2 NH H H H 2 H 2 NH H H H 3 H

TABLE 42

(R⁸)_(r) R⁵ R⁶ p R⁷ H H H 0 H H H H 1 H H H H 2 H H H H 3 H

TABLE 43

(R⁸)_(r) R⁵ R⁶ p R⁷ 3-Br, 5-CF₃ H H 1 H 3-Br, 5-CF₃ H H 2 H 3-Br, 5-CF₃ H H 3 H 3-Cl, 5-CF₃ H H 1 H 3-Cl, 5-CF₃ H H 2 H 3-Cl, 5-CF₃ H H 3 H 3-F, 5-CF₃ H H 1 H 3-F, 5-CF₃ H H 2 H 3-F, 5-CF₃ H H 3 H 3,5-(CF₃)₂ H H 1 H 3,5-(CF₃)₂ H H 2 H 3,5-(CF₃)₂ H H 3 H 5-CF₃ H H 1 H 5-CF₃ H H 2 H 5-CF₃ H H 3 H

TABLE 44

(R⁸)_(r) R⁵ R⁶ p R⁷ C₆H₅ H H 0 H C₆H₅ H H 1 H C₆H₅ H H 2 H C₆H₅ H H 3 H C₆H₄(4-Cl) H H 0 H C₆H₄(4-Cl) H H 1 H C₆H₄(4-Cl) H H 2 H C₆H₄(4-Cl) H H 3 H C₆H₄(4-CF₃) H H 0 H C₆H₄(4-CF₃) H H 1 H C₆H₄(4-CF₃) H H 2 H C₆H₄(4-CF₃) H H 3 H C₆H₄(4-OCF₃) H H 0 H C₆H₄(4-OCF₃) H H 1 H C₆H₄(4-OCF₃) H H 2 H C₆H₄(4-OCF₃) H H 3 H C₆H₄(4-Br) H H 0 H C₆H₄(4-Br) H H 1 H C₆H₄(4-Br) H H 2 H C₆H₄(4-Br) H H 3 H

TABLE 45

(R⁸)_(r) R B R⁵ R⁶ p R⁷ H S S H H 1 H H S S H H 2 H H S O H H 1 H H S O H H 2 H H S NH H H 1 H H S NH H H 2 H H S S H H 2 H H S O H H 2 H 2-CF₃ S NH H H 2 H 2-CF₃ S S H H 2 H 2-CF₃ S O H H 2 H 3-CF₃ S NH H H 2 H 3-CF₃ S S H H 2 H 3-CF₃ S O H H 2 H 2-OCF₃ S NH H H 2 H 2-OCF₃ S S H H 2 H 2-OCF₃ S O H H 2 H 3-OCF₃ S NH H H 2 H 3-OCF₃ S S H H 2 H 3-OCF₃ S O H H 2 H 2-Cl S NH H H 2 H 2-Cl S S H H 2 H 2-Cl S O H H 2 H 3-Cl S NH H H 2 H 3-Cl S S H H 2 H 3-Cl S O H H 2 H 3-Cl S NH H H 2 H 2-Br S S H H 2 H 2-Br S O H H 2 H 2-Br S NH H H 2 H 3-Br S S H H 2 H 3-Br S O H H 2 H 3-Br S NH H H 2 H 3,4-(CH₃)₂ S S H H 2 H 3,4-(CH₃)₂ S O H H 2 H 3,4-(CH₃)₂ S NH H H 2 H 3-OCH₃ S S H H 2 H 3-OCH₃ S O H H 2 H 3-OCH₃ S NH H H 2 H 3-OCH₂CH₃ S S H H 2 H 3-OCH₂CH₃ S O H H 2 H 3-OCH₂CH₃ S NH H H 2 H 4-OCH₃ S S H H 2 H 4-OCH₃ S O H H 2 H 4-OCH₃ S NH H H 2 H 4-OCH₂CH₃ S S H H 2 H 4-OCH₂CH₃ S O H H 2 H 4-OCH₂CH₃ S NH H H 2 H 3-OCH(CH₃)₂ S S H H 2 H 3-OCH(CH₃)₂ S O H H 2 H 3-OCH(CH₃)₂ S NH H H 2 H 4-OCH(CH₃)₂ S S H H 2 H 4-OCH(CH₃)₂ S O H H 2 H 4-OCH(CH₃)₂ S NH H H 2 H H NH S H H 1 H H NH S H H 2 H 2-CH₃ NH S H H 1 H 2-CH₃ NH S H H 2 H 2-OCH₃ NH S H H 1 H 2-OCH₃ NH S H H 2 H 2-OCF₃ NH S H H 1 H 2-OCF₃ NH S H H 2 H 2-NO₂ NH S H H 1 H 2-NO₂ NH S H H 2 H 2-Cl NH S H H 1 H 2-Cl NH S H H 2 H 2-Br NH S H H 1 H 2-Br NH S H H 2 H 2-CH₃ NH O H H 1 H 2-CH₃ NH NH H H 2 H 2-OCH₃ NH O H H 1 H 2-OCH₃ NH NH H H 2 H 2-OCF₃ NH O H H 1 H 2-OCF₃ NH NH H H 2 H 2-Cl NH O H H 1 H 2-Cl NH NH H H 2 H 2-Br NH O H H 1 H 2-Br NH NH H H 2 H H O S H H 1 H H O O H H 1 H H O NH H H 1 H H O S H H 2 H H O O H H 2 H H O NH H H 2 H 2-Cl O S H H 2 H 2-Cl O O H H 2 H 2-Cl O NH H H 2 H 3-Cl O S H H 2 H 3-Cl O O H H 2 H 3-Cl O NH H H 2 H 2-CF₃ O S H H 2 H 2-CF₃ O O H H 2 H 2-CF₃ O NH H H 2 H 3-CF₃ O S H H 2 H 3-CF₃ O O H H 2 H 3-CF₃ O NH H H 2 H 2-OCF₃ O S H H 2 H 2-OCF₃ O O H H 2 H 2-OCF₃ O NH H H 2 H 3-OCF₃ O S H H 2 H 3-OCF₃ O O H H 2 H 3-OCF₃ O NH H H 2 H 2-NO₂ NH O H H 1 H 2-NO₂ NH NH H H 2 H

TABLE 46

(R⁸)_(r) R⁵ R⁶ p R⁷ H H H 1 H H H H 2 H

The aldehyde compound of the general formula [VI], which is an intermediate for use in the production of the present compounds, can be produced, for example, according to the following scheme 1:

wherein all variables are as defined above.

The compounds of the general formula [II] or [III], which are intermediate for use in the production of the present compounds, can be produced, for example, according to the following schemes 2 to 6:

The compounds of the general formula [VII], which are intermediates for use in the production of the present compounds, can be produced, for example, according to the following scheme 7:

The compounds of the general formula [IV] and the alcohol compounds of the general formula [V], which are intermediates for use in the production of the present compounds, can be produced, for example, according to the following scheme 8:

wherein L² is chlorine or bromine, L³ is mesyloxy or tosyloxy, and X is as defined above.

The compounds of the general formula [VIII] or [IX] wherein R¹ is R¹ ₁ (wherein R¹ ₁ is Q₁ or Q₂ in the definition of R¹), which are intermediates for use in the production of the present compounds, can be obtained from various commercial sources or can be produced, for example, according to the schemes 9 and 10 depicted below.

The aldehyde compounds of the general formula: A—CHO (wherein A is as defined above), which are the starting compounds in the production of the compounds [VIII] or [IX], can be obtained, for example, by the processes disclosed in the following references.

Furancarbaldehydes:

Zh. Org. Khim., 11, 1955;

Tetrahedron., 39, 3881;

Chem. Pharm. Bull., 28, 2846

Thiophenecarbaldehydes:

Tetrahedron., 32, 1403;

J. Org. Chem., 41, 2835;

Zh. Obshch. Khim., 34, 4010;

Bull. Soc. Chim. France., 479 (1963)

Pyrrolecarbaldehydes:

Beilstein., 21, 1279

Isothiazolecarbaldehydes:

J. Medicin. Chem., 13, 1208;

J. Chem. Soc., 446 (1964)

Pyrazolecarboaldehydes:

Chem. Ber., 97, 3407;

J. Chem. Soc., 3314 (1957)

Imidazolecarbaldehydes:

J. Pharm. Soc. Japan., 60, 184;

J. Amer. Chem. Soc., 71, 2444

Thiazolecarbaldehydes:

JP-A 59-206370/1984

Chem. Ab., 62, 7764d;

Chem. Ber., 101, 3872;

JP-A 59-206370/1984

Thiadiazolecarbaldehydes:

U.S. Pat. No. 1,113,705

wherein all the variables are each as defined above.

wherein all the variables are each as defined above.

The compounds of the general formula: A-L′ (wherein L′ is halogen (e.g., chlorine, bromine, iodine)) included in the compounds [XI], which are intermediates for use in the production of the present compounds, can be obtained from various commercial sources or can be produced, for example, according to the following scheme 11:

wherein A and L′ are each as defined above.

The compounds [X], [XII] or [XIII], which are intermediates for use in the production of the present compounds, can be produced, for example, according to the following schemes 12 and 13:

wherein all the variables are each as defined above.

*) J.Amer.Chem.Soc., 33, 440 (1905)

wherein M_(S) is mesyl; T_(S) is tosyl; R¹⁶ is a protecting group for alcohols (e.g., benzoyl); R¹⁷ is protected formyl (e.g., acetal); L¹ is hydroxy or L; and R², R³, R⁷, R¹⁰, R¹¹, R¹⁴, X, L, p and t are each as defined above.

wherein all the variables are each as defined above.

The present compounds are satisfactorily effective for the control of various noxious insects, mites and ticks, examples of which are as follows:

Hemiptera

Delphacidae such as Laodelphax striatellus, Nilaparvata lugens and Sogatella furcifera, Deltocephalidae such as Nephotettix cincticeps and Nephotettix virescens, Aphididae, Pentatotnidae, Aleyrodidae , Coccidae, Tin gidae, Psyllidae, etc.

Lepidoptera

Pyralidae such as Chilo suppressalis, Cnaphalocrocis medinialis, Ostrinia nubilalis, Parapediasia teterrella, Notarcha derogata and Plodia interpunctella, Noctuidae such as Spodoptera litura, Spodoptera exigua, Spodoptera littoralis, Pseudaletia separata, Mamestra brassicae, Agrotis ipsilon, Trichoplusia spp., Heliothisspp., Helicoverpa spp. and Earias spp., Pieridae such as Pieris rapae crucivora, Tortricidae such as Adoxophyes spp., Grapholita molesta and Cydia pomonella, Carposinidae such as Carposinia niponensis, Lyonetiidae such as Lyonetin spp., Lymantriidae such as Lymantria spp. and Euproctis spp., Yponomeutidae such as Plutella xylostella, Gelechiidae such as Pectinophora gossypiella, Arctiidae such as Hyphantria cunen, Tineidae such as Tinea translucens and Tineola bisselliella, etc.

Diptera

Culex such as Culex pipiens pallens and Cules tritaeniorhynchus, Aedes such as Aedes albopictus and Aedes aegypti, Anopheles such as Anophelinae sinensis, Chironomidae, Muscidae such as Musca domestica and Muscina stabulans, Calliphoridae, Sarcophagidae, Fannia canicularis, Anthomyiidae such as Delia Platura and Delia antigua, Trypetidae, Drosophilidae, Psycllodidae, Tabanidae, Simuliidae, Stomoxyinae, etc.

Coleoptera

Diabrotica such as Diabrotica virgifera and Diabrotica undecimpunctata, Scarabaeidae such as Anomala cuprea and Anomala rufocuprea, Curculionidae such as Lissorphoptrus oryzophilus, Hypera pastica, and Calosobruchys chinensis, Tenebrionidae such as Tenebrio molitor and Tribolium castaneum, Chrysomelidae such as Phyllotreta striolata and Aulacophora femoralis, Anobiidae, Epilachna spp. such as Henosepilachna vigintioctopunctata, Lyctidae, Bostrychidae, Cerambycidae, Paederus fuscipes, etc.

Dictyoptera

Blattella germanica, Periplaneta fuliginosa, Peroplaneta americania, Periplaneta bnrnnea, Blatta orien talis, etc.

Thysanoptera

Thrips palmi, Thrips hawaiiensis, etc.

Hymenoptera

Formicidae, Vespidae, Bethylidae, Tenthredinidae such as Athalia rosae japonensis, etc.

Orthoptera

Gryllotalpidae, Acrididae, etc.

Siphonaptera

Purex irritans, etc.

Anoplura

Pedicuilus humanus capitis, Phthirus pubis, etc.

Isoptera (termites)

Reticulitermes speratus, Coptotermes formnosatitts, etc.

Acarina

plant patasitic Tetran)chidae such as Tetranychus uriticae, Panonychus citri, Tetranychus cinnabarinus and Panonychus ulmi, animal parasitic Ixodidae such as Boophilus microphis, house dust mites, etc.

The present compounds are also effective for the control of various noxious insects, mites and ticks having resistance to conventional insecticides and acaricides.

When the present compound is used as an active ingredient of insecticidal/acaricidal agents, it may be used as such without any addition of other ingredients. The present compound is, however, usually formulated into a dosage form such as oil sprays, emulsifiable concentrates, wettable powders, flowables, granules, dusts, aerosols, fumigants (foggings) and poison baits. These formulations are usually prepared by mixing the present compound with a solid carrier, a liquid carrier, a gaseous carrier or a bait, and if necessary, adding a surfactant and other auxiliaries used for formulation.

Each of the formulations usually contains the present compound as an active ingredient in an amount of 0.01% to 95% by weight.

Examples of the solid carrier to be used for the formulation are fine powder or granules of clay materials such as kaolin clay, diatomaceous earth, synthetic hydrated silicon oxide, bentonite, Fubasami clay and acid clay; various kinds of talc, ceramics, other inorganic minerals such as sericite, quartz, sulfur, active carbon, calcium carbonate and hydrated silica; and chemical fertilizers such as ammonium sulfate, ammonium phosphate, ammonium nitrate, urea and ammonium chloride.

Examples of the liquid carrier are water; alcohols such as methanol and ethanol; ketones such as acetone and methyl ethyl ketone; aromatic hydrocarbons such as benzene, toluene, xylene, ethylbenzene and methylnaphthalene; aliphatic hydrocarbons such as hexane, cyclohexane, kerosine and gas oil; esters such as ethyl acetate and butyl acetate; nitriles such as acetonitrile and isobutyronitrile; ethers such as diisopropyl ether and dioxane; acid amides such as N,N-dimethylformamide and N,N-dimethylacetamide; halogenated hydrocarbons such as dichloromethane, trichloroethane and carbon tetrachloride; dimethyl sulfoxide; and vegetable oils such as soybean oil and cottonseed oil.

Examples of the gaseous carrier or propellant are flon gas, butane gas, LPG (liquefied petroleum gas), dimethyl ether and carbon dioxide.

Examples of the surfactant are alkyl sulfates, alkyl sulfonates, alkyl arylsulfonates, alkyl aryl ethers and their polyoxyethylene derivatives, polyethylene glycol ethers, polyhydric alcohol esters and sugar alcohol derivatives.

Examples of the auxiliaries used for formulation, such as fixing agents or dispersing agents, are casein, gelatin, polysaccharides such as starch, gum arabic, cellulose derivatives and alginic acid, lignin derivatives, bentonite, sugars, and synthetic water-soluble polymers such as polyvinyl alcohol, polyvinyl pyrrolidone and polyacrylic acid.

Examples of the stabilizer are PAP (isopropyl acid phosphate), BHT (2,6-di-tert-butyl-4-methylphenol), BHA (mixtures of 2-t-butyl-4-methoxyphenol and 3-tert-butyl-4-methoxyphenol), vegetable oils, mineral oils, surfactants, fatty acids and their esters.

Examples of the base material to be used in the poison baits are bait materials such as grain powder, vegetable oils, sugars and crystalline cellulose; antioxidants such as dibutylhydroxytoluene and nordihydroguaiaretic acid; preservatives such as dehydroacetic acid; substances for preventing erroneous eating, such as red pepper powder, attractant flavors such as cheese flavor or onion flavor.

The formulation thus obtained is used as such or after diluted with water. The formulation may also be used in combination with other insecticides, nematocides, acaricides, bactericides, fungicides, herbicides, plant growth regulators, synergists, fertilizers, soil conditioners and/or animal feed under non-mixing conditions or premixing conditions.

Examples of the insecticide, acaricide and/or nematocide which can be used are organophosphorus compounds such as Fenitrothion [(O,O-dimethyl O-(3-methyl-4-nitrophenyl)phosphorothioate], Fenthion [O,O-dimethyl O-(3-methyl-4-methylthio)phenyl)phophorothioate], Diazinon [O,O-diethyl-O-2-isopropyl-6-methylpyrimidin-4-ylphosphorothioate], Chlorpyriphos [O,O-diethyl-O-3,5,6-trichloro-2-pyridylphosphorothioate], Acephate [O,S-dimethylacetylphosphoramidothioate], Methidachion [S-2,3-dihydro-5-methoxy-2-oxo-1,3,4-thiadiazol-3-ylmethyl O,O-dimethylphosphorodithioate], Disulfoton [O,O-diethyl S-2-ethylthioethylphosphorothioate], DDVP [2,2-dichlorovinyldimethylphosphate], Sulprofos [O-ethyl O-4-(methylthio)phenyl S-propyl phosphorodithioate], Cyanophos [O-4-cyanophenyl O,O-dimethylphosphorothioate], Dioxabenzofos [2-methoxy-4H-1,3,2-benzodioxaphosphinin-2-sulfide], Dimethoate [O,O-dimethyl-S-(N-methylcarbamoylmethyl)dithiophosphate], Phenthoate [ethyl 2-dimethoxyphosphinothioylthio(phenyl)acetate], Malathion [diethyl(dimethoxyphosphinothioylthio)succinate], Trichlorfon [dimethyl 2,2,2-trichloro-1-hydroxyethylphosphonate], Azinphos-methyl [S-3,4-dihydro-4-oxo-1,2,3-benzotriazin-3-ylmethyl-O,O-dimethylphosphorodithioate], Monocrotophos [dimethyl (E)-1-methyl-2-(methylcarbamoyl)vinylphosphate], Ethion [O,O,O′,O′-tetraethyl S,S′-methylenebis(phosphorodithioate)] and Profenfos [O-4-bromo-2-chlorophenyl O-ethyl S-propylphosphorothioate]; carbamate compounds such as BPMC [2-secbutylphenylmethylcarbamate], Benfuracarb [ethyl N-[2,3-dihydro-2,2-dimethylbenzofuran-7-yloxycarbonyl(methyl)aminothio]-N-isopropyl-β-alaninate], Propoxur [2-isopropoxyphenyl N-methylcarbamate], Carbosulfan [2,3-dihydro-2,2-dimethyl-7-benzo[b]-furanyl N-dibutylaminothio-N-methylcarbamate], Carbaril [1-naphthyl-N-methylcarbamate], Methomyl [S-methyl-N-[(methylcarbamoyl)oxy]thioacetoimidate], Ethiofencarb [2-(ethylthiomethyl)phenylmethylcarbamate], Aldicarb [2-methyl-2-(methylthio)propanaldehyde O-methylcarbamoyloxime], Oxamyl [N,N-dimethyl-2-methylcarbamoyloxyimino-2-(methylthio)acetamide], Alanylcarb [ethyl (Z)-N-benzyl-N-{[methyl(1-methylthioethylideneaminooxycarbonyl)amino]thio}-β-alanylate], Fenothiocarb [S-(4-phenoxybutyl)-N,N-dimethylthiocarbamate] and Thiodicarb [3,7,9,13-tetramethyl-5,11-dioxa-2,8,14-trithia-4,7,9,12-tetraazapentadeca-3,12-dien-6,10-dione]; pyrethroid compounds such as Etofenprox [2-(4-ethoxyphenyl)-2-methylpropyl-3-phenoxybenzylether], Fenvalerate [(RS)-α-cyano-3-phenoxybenzyl (RS)-2-(4-chlorophenyl)-3-methylbutyrate], Esfenvalerate [(S)-α-cyano-3-phenoxybenzyl (S)-2-(4-chlorophenyl)-3-methylbutyrate], Fenpropathrin [(RS)-α-cyano-3-phenoxybenzyl 2,2,3,3-tetramethylcyclopropanecarboxylate], Cypermethrin [(RS)-α-cyano-3-phenoxybenzyl (1RS,3RS)-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate], Permethrin [3-phenoxybenzyl (1RS,3RS)-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate], Cyhalothrin [(RS)-α-cyano-3-phenoxybenzyl (Z)-(1RS,3RS)-3-(2-chloro-3,3,3-trifluoropropenyl)-2,2-dimethylcyclopropanecarboxylate], Deltamethrin [(S)-α-cyano-m-phenoxybenzyl (1R,3R)-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropanecarboxylate], Cycloprothrin [(RS)-α-cyano-3-phenoxybenzyl (RS)-2,2-dichloro-1-(4-ethoxyphenyl)cyclopropanecarboxylate], Fluvalinate [α-cyano-3-phenoxybenzyl N-(2-chloro-α,α,α-trifluoro-p-tolyl)-D-valinate], Bifenthrin [2-methylbiphenyl-3-ylmethyl)(Z)-(1RS)-cis-3-(2-chloro-3,3,3-trifluoropropen-1-yl)-2,2-dimethylcyclopropanecarboxylate], Acrinathrin [cyano-(3-phenoxyphenyl)methyl [1R-{1α(S*),3α(Z)}]-2,2-diethyl-3-[3-oxo-3-(2,2,2-trifluoro-1-(trifluoromethyl)ethoxy-1-propenyl]cyclopropanecarboxylate], 2-methyl-2-(4-bromodifluoromethoxyphenyl)propyl (3-phenoxybenzyl) ether, Traromethrin [(S)-α-cyano-3-phenoxylbenzyl (1R, 3R)-3-[(1′RS)(1′,1′,2′,2′-tetrabromoethyl)]-2,2-dimethylcyclopropanecarboxylate] and Silafluofen [4-ethoxylphenyl [3-(4-fluoro-3-phenoxyphenyl)propyl]dimethylsilane]; thiadiazine derivatives such as Buprofezin [2-tert-butylimino-3-isopropyl-5-phenyl-1,3,5-thiadiazin-4-one]; nitroimidazolidine derivatives such as Imidacloprid [1-(6-chloro-3-pyridylmethyl)-N-nitroimidazolidin-2-ylidenamine]; Nereistoxin derivatives such as Cartap [S,S ′-(2-dimethylaminotrimethylene)bisthiocarbamate], Thiocyclam [N,N-di-methyl-1,2,3-trithian-5-ylamine] and Bensultap [S,S′-2-dimethylaminotrimethylene di-(benzenethiosulfonate)]; N-cyanoarmidine derivatives such as acetamiprid [N-cyano-N′-methyl-N′-(6-chloro-3-pyridylmethyl)acetamidine]; chlorinated hydrocarbons such as Endosulfan [6,7,8,9,10,10-hexachloro-1,5,5a,6,9,9a-hexahydro-6,9-methano-2,4,3-benzodioxathiepinoxide], γ-BHC [1,2,3,4,5,6-hexachlorocyclohexane] and Kelthane [1,1-bis(chlorophenyl)-2,2,2-trichloroethanol]; benzoylphenylurea compounds such as Chlorfluazuron [1-(3,5-dichloro-4-(3-chloro-5-trifluoromethylpyridin-2-yloxy)phenyl)-3-(2,6-difluorobenzoyl)urea], Teflubenzuron [1-(3,5-dichloro-2,4-difluorophenyl)-3-(2,6-difluorobenzoyl)urea] and Fulphenoxron [1-(4-(2-chloro-4-trifluoromethylphenoxy)-2-fluorophenyl)-3-(2,6-difluorobenzoyl)urea]; formamidine derivatives such as Amitraz [N,N′-[(methylimino)dimethylidine]-di-2,4-xylidine] and Chlordimeform [N′-(4-chloro-2-methylphenyl)-N,N-dimethylmethanimidamide]; thiourea derivatives such as Diafenthiuron [N-(2,6-diisopropyl-4-phenoxyphenyl)-N′-tert-butylcarbodiimide]; Fipronyl [5-amino-1-(2,6-dichloro-α,α,α-trifluoro-p-tolyl)-4-trifluoromet hylsulfinylpyrazole-3-carbonitrite], Tebfenozide [N-tert-butyl-N′-(4-ethylbenzoyl)-3,5-dimethylbenzohydrazide], 4-bromo-2-(4-chlorophenyl)-1-ethoxymethyl-5-trifluoromethylpyrrole-3-carbonitrile, Chlorfenapyl [4-bromo-2-(4-chlorophenyl)-1-ethoxymethyl-S-trifluoromethylpyrole-3-carbonitril], Bromopropylate [isopropyl 4,4′-dibromobenzylate], Tetradifon [4-chlorophenyl-2,4,5-trichlorophenyl sulfone], Quinomethionate [S,S-6-methylquinoxaline-2,3-diyldithiocarbonate], Propargite [2-(4-tert-butylphenoxy)cyclohexyl prop-2-yl sulfite], Fenbutatin oxide [bis[tris(2-methyl-2-phenylpropyl)tin)oxide], Hexythiazox [(4RS,5RS)-5-(4-chlorophenyl)-N-chlorohexyl-4-methyl-2-oxo-1,3-thiazolidine-3-carboxamide], Chlofentezine [3,6-bis(2-chlorophenyl)-1,2,4,5-tetrazine], Pyridaben [2-tert-butyl-5-(4-tert-butylbenzylthio)-4-chloropyridazin-3(2H)-one], Fenpyroximate [tert-butyl-(E)-4-[(1,3-dimethyl-5-phenoxypyrazol-4-yl)methyleneaminooxymethyl]benzoate], Tebfenpyrad [N-4-tert-butylbenzyl)-4-chloro-3-ethyl-1-methyl-5-pyrazol carboxamide], polynactin complexes including tetranactin, dinactin and trinactin; Milbemectin, Avermectin, Ivermectin, Azadilactin [AZAD], Pyrimidifen [5-chloro-N-[2-{4-(2-ethoxyethyl)-2,3-dimethylphenoxy}ethyl]-6-ethylpyrimidin-4-amine] and Pimetrozine [2,3,4,5-tetrahydro-3-oxo-4-[(pyridin-3-yl)-methyleneatnino]-6-methyl-1,2,4-triazine].

When the present compound is used as an active ingredient of insecticidal/acaricidal agents for agriculture, the application amount thereof is usually in the range of 0.1 to 100 g per 10 ares. In the case of emulsifiable concentrates, wettable powders and flowable concentrates, which are used after diluted with water, the application concentration thereof is usually in the range of 0.1 to 500 ppm. In the case of granules and dusts, they are applied as such without any dilution. When the present compound is used as an active ingredient of insecticidal/acaricidal agents for epidemic prevention, it is formulated into a dosage form such as emulsifiable concentrates, wettable powders and flowable concentrates, which are applied after diluted with water to a typical concentration of 0.1 to 500 ppm; or it is formulated into a dosage form such as oil sprays, aerosols, fumigants and poisonous baits, which are applied as such without any dilution.

The application amount and application concentration may vary depending upon various conditions such as formulation type, application time, place and method, kind of noxious insects, mites and ticks, and degree of damage, and they can be increased or decreased without limitation to the above range.

The present invention will be further illustrated by the following production examples, formulation examples and test examples, which are not to be construed to limit the scope thereof.

The following are production examples for the present compounds according to various production processes.

PRODUCTION EXAMPLE 1 Production of Compound (10) by Production Process E

To a solution of 0.44 g of 4-(3,3-dichloro-2-propenyloxy)-2,6-dichlorophenol, 0.20 g of 2-(2-hydroxyethyl)thiophene and 0.40 g of triphenylphosphine dissolved in 10 ml of tetrahydrofuran was added dropwise a solution of 0.31 g of diisopropyl azodicarboxylate dissolved in 5 ml of tetrahydrofuran, while stirring at room temperature. After stirring at room temperature for 12 hours, the reaction mixture was concentrated, to which 20 ml of diethyl ether was added, and the precipitate was filtered. The filtrate was concentrated, and the residue was subjected to silica gel chromatography, which afforded 0.38 g of 3,5-dichloro-4-(2-(2-thienyl)ethoxy)-1-(3,3-dichloro-2-propenyloxy)benzene (62% yield), n_(D) ^(25.6) 1.5919.

PRODUCTION EXAMPLE 2 Production of Compound (1) by Production Process D

To a mixture of 0.40 g of 2,6-dichloro-4-(3,3-dichloro-2-propenyloxy)phenol, 0.21 g of potassium carbonate and 20 ml of N,N-dimethylformamide was added dropwise a solution of 0.25 g of 6-chloro-3-(chloromethyl)pyridine dissolved in 5 ml of N,N-dimethylformamide, while stirring at room temperature. After stirring at room temperature for 7 hours, the reaction mixture was poured into ice-water, and extracted twice with 50 ml of diethyl ether. The combined ether layer was washed with water, dried with anhydrous magnesium sulfate, and concentrated to obtain a crude product. The crude product was subjected to silica gel chromatography, which afforded 0.44 g of 3,5-dichloro-4-(6-chloro-3-pyridylmethyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene (77% yield), m.p. 93.3° C.

PRODUCTION EXAMPLE 3 Production of Compound (9) by Production Process E

To a solution of 0.43 g of 4-(3,3-dichloro-2-propenyloxy)-2,6-dichlorophenol, 0.16 g of 4-(hydroxymethyl)pyridine and 0.39 g of triphenylphosphine dissolved in 10 ml of tetrahydrofuran was added dropwise a solution of 0.30 g of diisopropyl azodicarboxylate dissolved in 5 ml of tetrahydrofuran, while stirring at room temperature. After stirring at room temperature for 12 hours, the reaction mixture was concentrated, to which 20 ml of diethyl ether was added, and the precipitate was filtered. The filtrate was concentrated, and the residue was subjected to silica gel chromatography, which afforded 0.29 g of 3,5-dichloro-4-(4-pyridylmethyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene (51% yield), m.p. 74.0° C.

PRODUCTION EXAMPLE 4 Production of Compound (25) by Production Process H

A reaction vessel was charged with 0.20 g of 3,5-dichloro-4-(3-bromopropyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene, 0.08 g of thiophene-2-carboxylic acid, 0.08 g of potassium carbonate and 10 ml of N,N-dimethylformamide. After stirring at room temperature for 12 hours, the reaction mixture was poured into water, and extracted twice with 30 ml of diethyl ether. The combined ether layer was washed with water, dried with anhydrous magnesium sulfate, and concentrated to obtain a crude product. The crude product was subjected to silica gel chromatography, which afforded 0.18 g of 3,5-dichloro-4-(3-(thiophene-2-carboxylate)propyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene (81% yield), n_(D) ^(24.6) 1.5814.

PRODUCTION EXAMPLE 5 Production of Compound (29) by Production Process E

To a mixture of 0.4 g of 2-[2-(4-chlorophenyl)-1,3-dioxolan-4-yl]ethanol, 0.46 g of triphenylphosphine and 6 ml of tetrahydrofuran was added dropwise 0.35 ml of diisopropyl azodicarboxylate, while stirring at room temperature. After further stirring for 15 minutes, a solution of 0.5 g of 4-(3,3-dichloro-2-propenyloxy)-2,6-dichlorophenol in 2 ml of tetrahydrofuran was added. After stirring continued at room temperature for 3 hours, the reaction mixture was concentrated, and the residue was subjected to silica gel chromatography, which afforded 0.3 g of 3,5-dichloro-1-(3,3-dichloro-2-propenyloxy)-4-[2-[2-(4-chlorophenyl)-1,3-dioxolan-4-yl]ethoxy]benzene (35% yield), m.p. 84.1° C.

PRODUCTION EXAMPLE 6 Production of Compound (45) by Production Process E

To a solution of 0.33 g of 2-(3-hydroxypropyloxy)-5-trifluoromethylpyridine, 0.40 g of 2-chloro-6-methyl-4-(3,3-dichloro-2-propenyloxy)phenol and 0.41 g of triphenylphosphine dissolved in 30 ml of dichloromethane was added dropwise a solution of 0.32 g of diisopropyl azodicarboxylate dissolved in 3 ml of dichloromethane, while stirring at room temperature. After stirring at room temperature for 24 hours, the reaction mixture was concentrated to obtain a residue. The residue was subjected to silica gel chromatography, which afforded 0.56 g of 3-chloro-5-methyl-4-[3-(5-trifluoromethyl-2-pyridyloxy)propyloxy]-1-(3,3-dichloro-2-propenyloxy)benzene (92% yield), n_(D) ^(23.6) 1.5294.

PRODUCTION EXAMPLE 7 Production of Compound (46) by Production Process E

To a solution of 0.26 g of 2-(4-hydroxybutyloxy)-5-trifluoromethylpyridine, 0.3 g of 2-chloro-6-methyl-4-(3,3-dichloro-2-propenyloxy)phenol and 0.31 g of triphenylphosphine dissolved in 30 ml of dichloromethane was added dropwise a solution of 0.24 g of diisopropyl azodicarboxylate dissolved in 5 ml of dichloromethane, while stirring at room temperature. After stirring at room temperature for 24 hours, the reaction mixture was concentrated to obtain a residue. The residue was subjected to silica gel chromatography, which afforded 0.50 g of 3-chloro-5-methyl-4-[4-(5-trifluoromethyl-2-pyridyloxy)butyloxy]-1-(3,3-dichloro-2-propenyloxy)benzene (89% yield), n_(D) ^(23.0) 1.5275.

PRODUCTION EXAMPLE 8 Production of Compound (47) by Production Process A

In 10 ml of N,N-dimethylformamide were dissolved 0.7 g of 3-ethyl-5-methyl-4-[3-(5-trifluoromethyl-2-pyridyloxy)propyloxy]phenol and 0.27 g of potassium carbonate, to which a solution of 0.34 g of 1,1,3-trichloropropene dissolved in 5 ml of N,N-dimethylformamide was added dropwise, while stirring at room temperature. After stirring at room temperature for 12 hours, the reaction mixture was poured into ice-water, and extracted twice with 100 ml of diethyl ether. The combined diethyl ether was washed with water, dried with anhydrous magnesium sulfate, and concentrated to obtain a crude product. The crude produce was subjected to silica gel chromatography, which afforded 0.6 g of 3-ethyl-1-methyl-4-[3-(5-trifluoromethyl-2-pyridyloxy)propyloxy]-1-(3,3-dichloro-2-propenyloxy)benzene (65% yield), n_(D) ^(23.0) 1.5188.

PRODUCTION EXAMPLE 9 Production of Compound (48) by Production Process A

In 10 ml of N,N-dimethylformamide were dissolved 0.6 g of 3-ethyl-5-methyl-4-[4-(5-trifluoromethyl-2-pyridyloxy)butyloxy]phenol and 0.23 g of potassium carbonate, to which a solution of 0.28 g of 1,1,3-trichloropropene dissolved in 5 ml of N,N-dimethylformamide was added dropwise, while stirring at room temperature. After stirring at room temperature for 12 hours, the reaction mixture was poured into ice-water, and extracted twice with 100 ml of diethyl ether. The combined diethyl ether was washed with water, dried with anhydrous magnesium sulfate, and concentrated to obtain a crude product. The crude produce was subjected to silica gel chromatography, which afforded 0.50 g of 3-ethyl-5-methyl-4-[4-(5-trifluoromethyl-2-pyridyloxy)butyloxy]-1-(3,3-dichloro-2-propenyloxy)benzene (64% yield), n_(D) ^(23.0) 1.5170.

PRODUCTION EXAMPLE 10 Production of Compound (50) by Production Process A

In 10 ml of N,N-dimethylformamide were dissolved 0.45 g of 3,5-diethyl-4-[3-(5-trifluoromethyl-2-pyridyloxy)propyloxy]phenol and 0.17 g of potassium carbonate, to which a solution of 0.18 g of 1,1,3-trichloropropene dissolved in 5 ml of N,N-dimethylformamide was added dropwise, while stirring at room temperature. After stirring at room temperature for 12 hours, the reaction mixture was poured into ice-water, and extracted twice with 100 ml of diethyl ether. The combined diethyl ether was washed with water, dried with anhydrous magnesium sulfate, and concentrated to obtain a crude product. The crude produce was subjected to silica gel chromatography, which afforded 0.35 g of 3,5-diethyl-4-[3-(5-trifluoromethyl-2-pyridyloxy)propyloxy]-1-(3,3-dichloro-2-propenyloxy)benzene (60% yield), n_(D) ^(20.0) 1.5192.

PRODUCTION EXAMPLE 11 Production of Compound (49) by Production Process H

A mixture of 1.0 g of 1-(3-bromopropyloxy)-2,6-dichloro-4-(3,3-dichloro-2-propenyloxy)benzene and 4.0 g of 2-amino-5-(trifluoromethyl)pyridine was stirred at 90° C. for 3 hours. The reaction mixture was cooled to room temperature, and subjected to silica gel chromatography, which afforded 0.14 g of 3,5-dichloro-1-(3,3-dichloro-2-propenyloxy)-4-(3-(5-(trifluoromethyl)-2-pyridylamino)propyloxy)benzene (12% yield), n_(D) ^(25.0) 1.5525.

PRODUCTION EXAMPLE 12 Production of Compound (36) by Production Process A

A mixture of 0.5 g of 3,5-dichloro-4-[3-(5-trifluoromethylpyridin-2-yloxy)propyloxy]phenol, 0.25 g of 1,1,3-trichloropropene, 0.2.g of potassium carbonate and 3 ml of N,N-dimethylformamide was stirred at room temperature overnight. The reaction mixture was subjected to silica gel chromatography, which afforded 0.3 g of 3,5-dichloro-1-(3,3-dichloro-2-propenyloxy)-4-[3-(5-trifluoromethylpyridin-2-yloxy)propyloxy]benzene (47% yield), n_(D) ^(20.5) 1.5377.

PRODUCTION EXAMPLE 13 Production of Compound (36) by Production Process F

First, 2-(3-methanesulfonyloxypropyloxy)-5-trifluoromethylpyridine was prepared as follows.

A mixture of 12.6 g of 1,3-propanediol and 100 ml of N,N-dimethylformamide was stirred under a nitrogen stream, to which 3.30 g of an oily mixture containing 60% sodium hydride was added in small portions at room temperature over 30 minutes. After further stirring continued at room temperature for 1 hour, 20 ml of a DMF solution of 10.0 g of 2-chloro-5-trifluoromethylpyridine was added dropwise over 40 minutes. After further stirring continued under a nitrogen stream at room temperature overnight, 100 ml of about 2 N diluted hydrochloric acid was added over 15 minutes to stop the reaction. The reaction mixture was extracted twice with toluene at a total volume of 500 ml. The combined toluene layer was successively washed with diluted hydrochloric acid and aqueous sodium bicarbonate solution, dried with magnesium sulfate, and concentrated to obtain an oily product. The oily product was dissolved in 300 ml of hexane by heating, followed by recrystallization, which afforded 5.3 g of 2-(3-hydroxypropyloxy)-5-trifluoromethylpyridine as almost pure crystals (44% yield), m.p. 46.6° C.

A mixture of 4.0 g of 2-(3-hydroxypropyloxy)-5-trifluoromethylpyridine, 3.4 ml of triethylamine and 25 ml of toluene was vigorously stirred under a nitrogen stream, while cooling in chilled water bath to 5° C. Then, 1.63 g of methanesulfonyl chloride was added dropwise to this mixture at such a rate that the reaction temperature did not exceed 10° C., and the chilled water bath was removed. After further stirring continued at room temperature for 1.5 hours, 250 ml of water was added thereto, and the mixture was vigorously stirred for further 30 minutes, followed by phase separation. The toluene layer was washed once with water, dried with magnesium sulfate, and concentrated, which afforded 5 g of 2-(3-methanesulfonyloxypropyloxy)-5-trifluoromethylpyridine as an oily product (92% yield).

¹H-NMR δ(ppm) [CDCl₃, TMS] 8.39 (1H, br, s), 7.75 (1H, dd), 6.80 (1H, d), 4.0-5.0 (4H), 3.00 (3H, s), 2.30 (2H, quint.)

A mixture of 5 g of 2-(3-methanesulfonyloxypropyloxy)-5-trifluoromethylpyridine, 5 g of 4-(3,3-dichloro-2-propenyloxy)-2,6-dichlorophenol, 2.64 g of potassium carbonate and 300 ml of N,N-dimethylformamide was vigorously stirred at room temperature for 4 days. Then, 300 ml of 2 N hydrochloric acid was added to this mixture, and extracted twice with toluene at a total volume of 300 ml. The combined toluene layer was successively washed with 2 N hydrochloric acid and aqueous sodium bicarbonate solution, dried with magnesium sulfate, and concentrated to obtain about 8 g of an oily product. The oily product was subjected to silica gel chromatography, which afforded 6.0 g of 3,5-dichloro-1-(3,3-dichloro-2-propenyloxy)-4-[3-(5-trifluoromethylpyridin-2-yloxy)propyloxy]benzene (70% yield).

The following are specific examples of the present compound under the corresponding compound numbers with their physical properties, if measured.

(1) 3,5-Dichloro-4-(6-chloro-3-pyridylmethyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene m.p. 93.3° C.

(2) 3,5-Dichloro-4-(2,6-dichloro-3-pyridylmethyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene m.p. 73.3° C.

(3) 3,5-Dichloro-4-(2-(1-pyrazolynyl)ethoxy)-1-(3,3-dichloro-2-propenyloxy)benzene m.p. 59.8° C.

(4) 3,5-Dichloro-4-(2-(1-pyrazolynyl)ethoxy)-1-(3,3-dibromo-2-propenyloxy)benzene m.p. 55.3° C.

(5) 3,5-Dichloro-4-(2-pyridylmethyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene m.p. 48.2° C.

(6) 3,5-Dichloro-4-(2-thienylmethyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene m.p. 44.6° C.

(7) 3,5-Dichloro-4-(2-furanylmethyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene m.p. 46.0° C.

(8) 3,5-Dichloro-4-(3-pyridylmethyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene m.p. 105.9° C.

(9) 3,5-Dichloro-4-(4-pyridylmethyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene m.p. 74.0° C.

(10) 3,5-Dichloro-4-(2-(2-thienyl)ethoxy)-1-(3,3-dichloro-2-propenyloxy)benzene n_(D) ^(25.6) 1.5919

(11) 3,5-Dichloro-4-(2-(3-methylthiazol-2-yl)ethoxy)-1-(3,3-dichloro-2-propenyloxy)benzene m.p. 30.4° C.

(12) 3,5-Dichloro-4-(2,4,5-trichloroimidazolynylmethyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene m.p. 67.5° C.

(13) 3,5-Dichloro-4-(3,5-dimethyl-4-isoxazolynylmethyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene m.p. 127.4° C.

(14) 3,5-Dichloro-4-(2-(3-thienyl)ethoxy)-1-(3,3-dichloro-2-propenyloxy)benzene n_(D) ^(24.0) 1.5916

(15) 3,5-Dichloro-4-(3-(4-pyridyl)propyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene n_(D) ^(24.0) 1.5566

(16) 3,5-Dichloro-4-((2-(1,4-benzodioxanyl))methoxy)-1-(3,3-dichloro-2-propenyloxy)benzene n_(D) ^(24.6) 1.5799

(17) 3,5-Dichloro-4-((2-(5-formyl)furanyl)methoxy)-1-(3,3-dichloro-2-propenyloxy)benzene m.p. 91.5° C.

(18) 3,5-Dichloro-4-((3-(6-methylpyridyl))methoxy)-1-(3,3-dichloro-2-propenyloxy)benzene m.p. 86.7° C.

(19) 3,5-Dichloro-4-(2-(4-pyridylthio)ethoxy)-1-(3,3-dichloro-2-propenyloxy)benzene m.p. 74.7° C.

(20) 3,5-Dichloro-4-(3-(3-pyridyl)propyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene m.p. 48.3° C.

(21) 3-(2,6-Dichloro-4-(3,3-dichloro-2-propenyloxy)phenoxy)propyl nicotinate n_(D) ^(22.2) 1.5674

(22) 3-(2,6-Dichloro-4-(3,3-dichloro-2-propenyloxy)phenoxy)propyl isonicotinate n_(D) ^(22.5) 1.5667

(23) 3-(2,6-Dichloro-4-(3,3-dichloro-2-propenyloxy)phenoxy)propyl quinolinate n_(D) ^(25.5) 1.6002

(24) 3-(2,6-Dichloro-4-(3,3-dichloro-2-propenyloxy)phenoxy)propyl 2-furanate n_(D) ^(24.0) 1.5589

(25) 3-(2,6-Dichloro-4-(3,3-dichloro-2-propenyloxy)phenoxy)propyl 2-thiophenate n_(D) ^(24.0) 1.5814

(26) 3-(2,6-Dichloro-4-(3,3-dichloro-2-propenyloxy)phenoxy)propyl 3-thiophenate n_(D) ^(24.0) 1.5788

(27) 3-(2,6-Dichloro-4-(3,3-dichloro-2-propenyloxy)phenoxy)propyl picolinate n_(D) ^(24.0) 1.5737

(28) 3-(2,6-Dichloro-4-(3,3-dichloro-2-propenyloxy)phenoxy)propyl 3-quinolinate m.p. 92.3° C.

(29) 3,5-Dichloro-4-(2-(2-((2-(4-chlorophenyl)-1,3-dioxanyl)))ethoxy)-1-(3,3-dichloro-2-propenyloxy)benzene m.p. 84.1° C.

(30) 3,5-Dichloro-4-(3-(2-pyridylthio)propyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene n_(D) ^(22.5) 1.5982

(31) 3,5-Dichloro-4-(2-(6-ethoxy-2-benzothiezolyl)ethoxy)-1-(3,3-dichloro-2-propenyloxy)benzene m.p. 80.6° C.

(32) 3,5-Dichloro-4-(2-(2-benzoxazolyl)ethoxy)-1-(3,3-dichloro-2-propenyloxy)benzene m.p. 61.2° C.

(33) 3,5-Dichloro-4-(2-methyl-2-(2-(6-chloro)pyridyloxy)propyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene n_(D) ^(22.5) 1.5742

(34) 3,5-Dichloro-4-(2-(N-phthalimido)ethoxy)-1-(3,3-dichloro-2-propenyloxy)benzene m.p. 115.2° C.

(35) 3,5-Dichloro-4-(3-(N-phthalimido)propyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene m.p. 78.4° C.

(36) 3,5-Dichloro-4-(3-(5-trifluoromethyl-2-pyridyloxy)propyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene n_(D) ^(20.5) 1.5377

(37) 3,5-Dichloro-4-(3-(3-chloro-5-trifluoromethyl-2-pyridyloxy)propyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene n_(D) ^(22.5) 1.5429

(38) 3,5-Dichloro-4-(3-(N-(1,2-dihydroxy-3-bromo-5-trifluoromethyl-2-oxo)pyridyl)propyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene m. p. 119.5° C.

(39) 3,5-Dichloro-4-(3-(2-benzimidazolylthio)propyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene m.p. 120.7° C.

(40) 3,5-Dichloro-4-(3-(2-benzothiazolylthio)propyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene n_(D) ^(22.5) 1.6322

(41) 3,5-Dichloro-4-(3-(5-trifluoromethyl-2-pyridyloxy)ethoxy)-1-(3,3-dichloro-2-propenyloxy)benzene m.p. 67.0° C.

(42) 3,5-Dichloro-4-(4-(5-trifluoromethyl-2-pyridyloxy)butyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene n_(D) ^(21.3) 1.5359

(43) 3,5-Dichloro-4-(5-(5-trifluoromethyl-2-pyridyloxy)pentyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene n_(D) ^(21.3) 1.5307

(44) 3,5-Dichloro-4-(6-(5-trifluoromethyl-2-pyridyloxy)hexyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene n_(D) ^(21.3) 1.5302

(45) 3-Chloro-5-methyl-4-(3-(5-trifluoromethyl-2-pyridyloxy)propyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene n_(D) ^(23.6) 1.5294

(46) 3-Chloro-5-methyl-4-(4-(5-trifluoromethyl-2-pyridyloxy)butyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene n_(D) ^(23.0) 1.5275

(47) 3-Ethyl-5-methyl-4-(3-(5-trifluoromethyl-2-pyridyloxy)propyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene n_(D) ^(23.0) 1.5188

(48) 3-Ethyl-5-methyl-4-(4-(5-trifluoromethyl-2-pyridyloxy)butyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene n_(D) ^(23.0) 1.5170

(49) 3,5-Dichloro-4-(3-(5-trifluoromethyl-2-pyridylamino)propyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene n_(D) ^(25.0) 1.5525

(50) 3,5-Diethyl-4-(3-(5-trifluoromethyl-2-pyridylamino)propyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene n_(D) ^(20.0) 1.5192

(51) 3,5-Diethyl-4-(4-(5-trifluoromethyl-2-pyridyloxy)butyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene

(52) 3,5-Dichloro-4-(4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)butyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene

(53) 3,5-Dichloro-4-(3-(3-bromo-5-trifluoromethyl-2-pyridyloxy)propyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene

(54) 3,5-Dichloro-4-(4-(3-bromo-5-trifluoromethyl-2-pyridyloxy)butyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene

(55) 3,5-Dichloro-4-(3-(3-fluoro-5-trifluoromethyl-2-pyridyloxy)propyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene

(56) 3,5-Dichloro-4-(4-(3-fluoro-5-trifluoromethyl-2-pyridyloxy)butyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene

(57) 3,5-Dichloro-4-(3-(3,5-bistrifluoromethyl-2-pyridyloxy)propyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene

(58) 3,5-Dichloro-4-(4-(3,5-bistrifluoromethyl-2-pyridyloxy)butyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene

(59) 3,5-Dibromo-4-(3-(5-trifluoromethyl-2-pyridyloxy)propyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene

(60) 3,5-Dibromo-4-(4-(5-trifluoromethyl-2-pyridyloxy)butyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene

(61) 3,5-Dichloro-4-(4-(5-trifluoromethyl-2-pyridylamino)butyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene

(62) 3,5-Diethyl-4-(3-(5-trifluoromethyl-2-pyridylamino)propyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene

(63) 3-Ethyl-5-methyl-4-(3-(5-trifluoromethyl-2-pyridylamino)propyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene

(64) 3-Chloro-5-methyl-4-(3-(5-trifluoromethyl-2-pyridylamino)propyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene

(65) 3,5-Diethyl-4-(4-(5-trifluoromethyl-2-pyridylamino)butyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene

(66) 3-Ethyl-5-methyl-4-(4-(5-trifluoromethyl-2-pyridylamino)butyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene

(67) 3-Chloro-5-methyl-4-(4-(5-trifluoromethyl-2-pyridylamino)butyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene

(68) 3,5-Dichloro-4-(2-(2-((2-(4-chlorophenyl)-1,3-dioxanyl)))ethoxy)-1-(3,3-dichloro-2-propenyloxy)benzene

(69) 3,5-Dichloro-4-(2-(2-((2-(4-trifluoromethylphenyl)-1,3-dioxanyl)))-ethoxy)-1-(3,3-dichloro-2-propenyloxy)benzene

(70) 3,5-Dichloro-4-(2-(2-((2-(4-trifluoromethoxyphenyl)-1,3-dioxanyl)))-ethoxy)-1-(3,3-dichloro-2-propenyloxy)benzene

(71) 3,5-Dichloro-4-(3-(2-pyridyloxy)propylamino)-1-(3,3-dichloro-2-propenyloxy)benzene m.p. 76.2° C.

The following are production examples for the intermediate compounds of the general formula [II] or [III].

Intermediate Production Example 1

A reaction vessel was charged with 5.0 g of 4-(benzyloxy)phenol and 100 ml of carbon tetrachloride, to which a solution 5.43 g of t-butyl hypochlorite dissolved in 5 ml of carbon tetrachloride was slowly added dropwise, while stirring under ice cooling. After 24 hours, the reaction mixture was poured into water, followed by phase separation. The organic layer (i.e., carbon tetrachloride layer) was washed with water, dried with anhydrous magnesium sulfate, and concentrated to obtain a crude product. The crude product was subjected to silica gel chromatography, which afforded 4.24 g of 2,4-dichloro-4-(benzyloxy)phenol (63% yield).

A reaction vessel was charged with 5.10 g of 1,3-dibromopropane, 2.40 g of potassium carbonate and 50 ml of N,N-dimethylformamide, to which a solution of 4.24 g of 2,6-dichloro-4-(benzyloxy)phenol dissolved in 10 ml of N,N-dimethylformamide was slowly added dropwise. After stirring at room temperature for 24 hours, the reaction mixture was poured into water, and extracted twice with 150 ml of diethyl ether. The combined ether layer was washed with water, dried with anhydrous magnesium sulfate, and concentrated to obtain a crude product. The crude product was subjected to silica gel chromatography, which afforded 4.24 g of 3,5-dichloro-4-(3-bromopropyloxy)-1-(benzyloxy)benzene (68% yield).

A reaction vessel was charged with 4.24 g of 3,5-dichloro-4-(3-bromopropyloxy)-1-(benzyloxy)benzene, 1.33 g of benzoic acid, 1.65 g of potassium carbonate and 20 ml of N,N-dimethylformamide. After stirring at room temperature for 24 hours, the reaction mixture was poured into water, and extracted twice with 150 ml of diethyl ether. The combined ether layer was washed with water, dried with anhydrous magnesium sulfate, and concentrated to obtain a crude product. The crude product was subjected to silica gel chromatography, which afforded 3.75 g of 3,5-dichloro-4-(3-benzoyloxypropyloxy)-1-(benzoyloxy)benzene (80% yield).

A reaction vessel was charged with 3.75 g of 3,5-dichloro-4-(3-benzoyloxypropyloxy)-1-(benzyloxy)benzene, 5.0 g of 10% aqueous potassium hydroxide solution and 50 ml of methanol. After stirring at room temperature for 24 hours, the reaction mixture was concentrated. The concentrate was poured into water, and extracted twice with 150 m of diethyl ether. The combined ether layer was washed with water, dried with anhydrous magnesium sulfate, and concentrated to obtain a crude product. The crude product was subjected to silica gel chromatography, which afforded 2.56 g of 3-(2,6-dichloro-4-(benzyloxy)phenoxy)-1-propyl alcohol (90% yield).

A mixture of 0.5 g of 3-(2,6-dichloro-4-(benzyloxy)phenoxy)-1-propyl alcohol thus obtained, 0.1 g of an oily mixture containing 60% sodium hydride, and 3 ml of N,N-dimethylformamide was stirred at room temperature for 1 hour. Then, 0.3 g of 2-chloro-5-trifluoromethylpyridine was added to this mixture, followed by heating to 100° C. After stirring continued for 1 hour, the mixture was poured into 50 m of ice-water, and extracted with toluene at a total volume of 50 ml. The combined toluene layer was successively washed with diluted hydrochloric acid and aqueous sodium bicarbonate solution, dried with magnesium sulfate, and concentrated. The residue was silica gel chromatography, which afforded 0.5 g of 1-benzyloxy-3,5-dichloro-4-[3-(5-trifluoromethylpyridin-2-yloxy)propyloxy]benzene (67% yield).

¹H-NMR δ(ppm) [CDCl₃, TMS] 8.44 (1H, br, s), 7.76 (1H, dd), 7.2-7.5 (5H), 6.90 (2H, s), 6.81 (1H, d), 5.00 (2H, s), 4.62 (2H, t), 4.11 (2H, t), 2.31 (2H, quint.).

A reaction vessel was charged with 0.5 g of 1-benzyloxy-3,5-dichloro-4-(3-(5-trifluoromethylpyridin-2-yloxy)propyloxy)benzene and 50 ml of ethyl acetate, and the air in the vessel was replaced with nitrogen. Then, 0.3 g of 10% palladium carbon was added, and the nitrogen in the vessel was replaced with hydrogen, followed by stirring at room temperature for 24 hours. The hydrogen in the vessel was replaced with nitrogen, after which the reaction mixture was filtered through Celite, and the filtrate was concentrated, which afforded 0.36 g of 3,5-dichloro-4-(3-(5-trifluoromethylpyridin-2-yloxy)propyloxy)phenol (92% yield).

¹H-NMR δ(ppm) [CDCl₃, TMS] 8.45 (1H, br, s), 7.75 (1H, dd), 6.77 (2H, s), 6.75 (1H, d), 4.60 (2H, t), 4.15 (2H, t), 2.25 (2H, quint.)

The following are specific examples of the intermediate compound of the general formula [II] or [III] under the corresponding compound numbers.

1) 3,5-Dichloro-4-(6-chloro-3-pyridylmethyloxy)phenol

2) 3,5-Dichloro-4-(2,6-dichloro-3-pyridylmethyloxy)phenol

3) 3,5-Dichloro-4-(2-(1-pyrazolynyl)ethoxy)phenol

4) 3,5-Dichloro-4-(2-pyridylmethyloxy)phenol

5) 3,5-Dichloro-4-(2-thienylmethyloxy)phenol

6) 3,5-Dichloro-4-(2-furanylmethyloxy)phenol

7) 3,5-Dichloro-4-(3-pyridylmethyloxy)phenol

8) 3,5-Dichloro-4-(4-pyridylmethyloxy)phenol

9) 3,5-Dichloro-4-(2-(2-thienyl)ethoxy)phenol

10) 3,5-Dichloro-4-(2(3-methylthiazol-2-yl)ethoxyphenol

11) 3,5-Dichloro-4-(2,4,5-trichloroimidazolynylmethyloxy)phenol

12) 3,5-Dichloro-4-(3,5-dimethyl-4-yloxazolynylmethyloxy)phenol

13) 3,5-Dichloro-4-(2-(3-thienyl)ethoxy)phenol

14) 3,5-Dichloro-4-(3-(4-pyridyl)propyloxy)phenol

15) 3,5-Dichloro-4-((2-(1,4-benzodioxanyl))methoxy)phenol

16) 3,5-Dichloro-4-((2-(5-formyl)furanyl)methoxy)phenol

17) 3,5-Dichloro-4-((3,(6-methylpyridyl))methoxy)phenol

18) 3,5-Dichloro-4-(2-(4-pyridylthio)ethoxy)phenol

19) 3,5-Dichloro-4-(3-(3-pyridyl)propyloxy)phenol

20) 3-(2,6-Dichloro-4-hydroxyphenoxy)propyl nicotinate

21) 3-(2,6-Dichloro-4-hydroxyphenoxy)propyl isonicotinate

22) 3-(2,6-Dichloro-4-hydroxyphenoxy)propyl quinolinate

23) 3-(2,6-Dichloro-4-hydroxyphenoxy)propyl 2-furanate

24) 3-(2,6-Dichloro-4-hydroxyphenoxy)propyl 2-thiophenate

25) 3-(2,6-Dichloro-4-hydroxyphenoxy)propyl 3-thiophenate

26) 3-(2,6-Dichloro-4-hydroxyphenoxy)propyl picolinate

27) 3-(2,6-Dichloro-4-hydroxyphenoxy)propyl quinolinate

28) 3,5-Dichloro-4-(2-(2-((2-(4-chlorophenyl)-1,3-dioxanyl)))ethoxy)phenol

29) 3,5-Dichloro-4-(3-(2-pyridylthio)propyloxy)phenol

30) 3,5-Dichloro-4-(2-(6-ethoxy-2-benzothiazolyl)ethoxy)phenol

31) 3,5-Dichloro-4-(2-(2-benzoxazolyl)ethoxy)phenol

32) 3,5-Dichloro-4-(2-methyl-2-(2-(6-chloro)pyridyloxy)propyloxy)phenol

33) 3,5-Dichloro-4-(2-(N-phthalimido)ethoxy)phenol

34) 3,5-Dichloro-4-(3-(N-phthalimido)propyloxy)phenol

35) 3,5-Dichloro-4-(3-(5-trifluoromethyl-2-pyridyloxy)propyloxy)phenol

36) 3,5-Dichloro-4-(3-(3-chloro-5-trifluoromethyl-2-pyridyloxy)propyloxy)phenol

37) 3,5-Dichloro-4-(3-(N-(1,2-dihydroxy-3-bromo-5-trifluoromethyl-2-oxo)pyridyl)propyloxy))phenol

38) 3,5-Dichloro-4-(3-(2-benzothiazolylthio)propyloxy)phenol

39) 3,5-Dichloro-4-(3-(2-benzothiazolylthio)propyloxy)phenol

40) 3,5-Dichloro-4-(2-(5-trifluoromethyl-2-pyridyloxy)ethoxy)phenol

41) 3,5-Dichloro-4-(4-(5-trifluoromethyl-2-pyridyloxy)butyloxy)phenol

42) 3,5-Dichloro-4-(5-(5-trifluoromethyl-2-pyridyloxy)pentyloxy)phenol

43) 3,5-Dichloro-4-(6-(5-trifluoromethyl-2-pyridyloxy)hexyloxy)phenol

44) 3-Chloro-5-methyl-4-(3-(5-trifluoromethyl-2-pyridyloxy)propyloxy)phenol

45) 3-Chloro-5-methyl-4-(4-(5-trifluoromethyl-2-pyridyloxy)butyloxy)phenol

46) 3-Ethyl-5-methyl-4-(3-(5-trifluoromethyl-2-pyridyloxy)propyloxy)phenol

47) 3-Ethyl-5-methyl-4-(4-(5-trifluoromethyl-2-pyridyloxy)butyloxy)phenol

48) 3,5-Dichloro-4-(3-(5-trifluoromethyl-2-pyridylamino)propyloxy)phenol

49) 3,5-Diethyl-4-(3-(5-trifluoromethyl-2-pyridyloxy)propyloxy)phenol

50) 3,5-Diethyl-4-(4-(5-trifluoromethyl-2-pyridyloxy)butyloxy)phenol

51) 3,5-Dichloro-4-(4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)butyloxy)phenol

52) 3,5-Dichloro-4-(3-(3-bromo-5-trifluoromethyl-2-pyridyloxy)propyloxy)phenol

53) 3,5-Dichloro-4-(4-(3-bromo-5-trifluoromethyl-2-pyridyloxy)butyloxy)phenol

54) 3,5-Dichloro-4-(3-(3-fluoro-5-trifluoromethyl-2-pyridyloxy)propyloxy)phenol

55) 3,5-Dichloro-4-(4-(4-fluoro-5-trifluoromethyl-2-pyridyloxy)butyloxy)phenol

56) 3,5-Dichloro-4-(3-(3,5-bistrifluoromethyl-2-pyridyloxy)propyloxy)phenol

57) 3,5-Dichloro-4-(4-(3,5-bistrifluoromethyl-2-pyridyloxy)butyloxy)phenol

58) 3,5-Dibromo-4-(3-(5-trifluoromethyl-2-pyridyloxy)propyloxy)phenol

59) 3,5-Dibromo-4-(4-(5-trifluoromethyl-2-pyridyloxy)butyloxy)phenol

60) 3,5-Dichloro-4-(4-(5-trifluoromethyl-2-pyridylamino)butyloxy)phenol

61) 3,5-Diethyl-4-(3-(5-trifluoromethyl-2-pyridylamino)propyloxy)phenol

62) 3-Ethyl-5-methyl-4-(3-(5-trifluoromethyl-2-pyridylamino)propyloxy)phenol

63) 3-Chloro-5-methyl-4-(3-(5-trifluoromethyl-2-pyridylamino)propyloxy)phenol

64) 3,5-Diethyl-4-(4-(5-trifluoromethyl-2-pyridylamino)butyloxy)phenol

65) 3-Ethyl-5-methyl-4-(4-(5-trifluoromethyl-2-pyridylamino)butyloxy)phenol

66) 3-Chloro-5-methyl-4-(4-(5-trifluoromethyl-2-pyridylamino)butyloxy)phenol

67) 3,5-Dichloro-4-(2-(2-((2-(4-chlorophenyl)-1,3-dioxanyl)))ethoxy)phenol

68) 3,5-Dichloro-4-(2-(2-((2-(4-trifluoromethylphenyl)-1,3-dioxanyl)))ethoxy)phenol

69) 3,5-Dichloro-4-(2-(2-((2-(4-trifluoromethoxyphenyl)-1,3-dioxanyl)))ethoxy)phenol

The following are production examples for the intermediate compounds of the general formula [VII].

Reference Production Example 1

A reaction vessel was charged with 30.5 g of 4-hydroxyphenyl benzoate, 21.6 g of potassium carbonate, 20.8 g of 1,1,3-trichloropropene and 100 ml of N,N-dimethylformamide. After stirring at room temperature for 15 hours, the reaction mixture was poured into water, and extracted twice with 50 ml of diethyl ether. The combined ether layer was washed with water, dried with anhydrous magnesium sulfate, and concentrated to obtain a crude product. The crude product was subjected to silica gel chromatography, which afforded 44.1 g of 4-(3,3-dichloro-2-propenyloxy)phenyl benzoate (96% yield).

A reaction vessel was charged with 44.1 g of 4-(3,3-dichloro-2-propenyloxy)phenyl benzoate and 400 ml of methanol, to which 33 g of 30% potassium hydroxide solution was slowly added dropwise under ice cooling. After stirring for 1 hour, the reaction mixture was made weakly acidic by the addition of 10% hydrochloric acid, and extracted twice with 150 ml of diethyl ether under salting out. The combined ether layer was washed with water, dried with anhydrous magnesium sulfate, and concentrated to obtain a crude product. The crude product was subjected to silica gel chromatography, which afforded 26.0 g of 4-(3,3-dichloro-2-propenyloxy)phenol (87% yield).

A reaction vessel was charged with 26.0 g of 4-(3,3-dichloro-2-propenyloxy)phenol and 500 ml of carbon tetrachloride, to which a solution of 27.1 g of tert-butyl hypochlorite dissolved in 20 ml of carbon tetrachloride was slowly added dropwise, while stirring under ice cooling. After 24 hours, the reaction mixture was poured into water, followed by phase separation. The organic layer (i.e., carbon tetrachloride layer) was washed with water, dried with anhydrous magnesium sulfate, and concentrated to obtain a crude product. The crude product was subjected to silica gel chromatography, which afforded 11.0 g of 2,6-dichloro-4-(3,3-dichloro-2-propenyloxy)phenol (32% yield), n_(D) ^(22.5) 1.5895.

Reference Production Example 2

A solution of 50 g of 4-bromo-6-chloro-2-methylphenol and 42.5 g of benzyl bromide dissolved in 200 ml of N,N-dimethylformamide was stirred at room temperature, to which 37.4 g of potassium carbonate was added, and the mixture was stirred for 12 hours. After completion of the reaction, the solvent was removed by distillation under reduced pressure, and the residue was added to 400 ml of diethyl ether, washed with water, dried with anhydrous magnesium sulfate, and concentrated to obtain a crude product. The crude product was subjected to silica gel chromatography, which afforded 63 g of 4-bromo-6-chloro-2-methyl-1-benzyloxybenzene (90% yield).

Then, 40 g of 4-bromo-6-chloro-2-methyl-1-benzyloxybenzene was dissolved in 400 ml of tetrahydrofuran, followed by stirring at −70° C., to which 76 ml of n-butyl lithium solution (in hexane, 1.69 mol/liter) was added dropwise, followed by further stirring at −70° C. for 2 hours. To this reaction mixture was added dropwise a solution of 13.3 g of trimethoxyborane dissolved in 50 ml of tetrahydrofuran. Then, the reaction mixture was stirred for 1 hours, while warming to room temperature, and 100 ml of 10% aqueous hydrochloric acid solution was added in small portions, followed by stirring for 20 minutes. The tetrahydrofuran layer was washed with water, dried with anhydrous magnesium sulfate, and concentrated. The residue was mixed with 200 ml of toluene, and heated at 70° C. under stirring, to which 36 ml of 30% aqueous hydrogen peroxide solution was added dropwise. After heating under reflux for 1 hour, the reaction mixture was washed once with water, twice with 10% ferrous sulfate and then ammonium water, and once with water, followed by phase separation. The toluene layer was dried with anhydrous magnesium sulfate, and concentrated to obtain a crude product. The crude product was subjected to silica gel chromatography, which afforded 29 g of 4-benzyloxy-3-chloro-5-methylphenol (91% yield).

To a solution of 27.3 g of 4-benzyloxy-3-chloro-5-methylphenol dissolved in 250 ml of chloroform and being stirred at 0° C. were added 15.4 g of benzoyl chloride and then 13.3 g of triethylamine. After stirring at room temperature for 2 hours, the chloroform layer was washed with water, dried with anhydrous magnesium sulfate, and concentrated. The residue was subjected to silica gel chromatography, which afforded 35 g of 4-benzyloxy-3-chloro-5-methyl-1-benzoyloxybenzene (90% yield).

A reaction vessel was charged with 35 g of 4-benzyloxy-3-chloro-5-methyl-1-benzoyloxybenzene and 200 ml of ethyl acetate, and the air in the vessel was replaced with nitrogen. Then, 2 g of 10% palladium carbon was added, and the nitrogen in the vessel was replaced with hydrogen, followed by vigorous stirring at room temperature for 10 hours. The hydrogen in the vessel was replaced with nitrogen, after which the reaction mixture was filtered, and the filtrate was concentrated. The residue was subjected to silica gel chromatography, which afforded 25 g of 4-benzoyloxy-2-chloro-6-methylphenol (96% yield).

Then, 25 g of 4-benzoyloxy-2-chloro-6-methylphenol was dissolved in 250 ml of chloroform, to which 12 g of chloromethyl methyl ether was added, while stirring at 0° C., and 21 g of N-ethyldiisopropylamine was added dropwise. After heating under reflux for 1 hour, the chloroform layer was washed with water, and concentrated. The residue was subjected to silica gel chromatography, which afforded 27.4 g of 3-chloro-4-methoxymethoxy-5-methyl-1-benzoyloxybenzene (96% yield).

Then, 26 g of 3-chloro-4-methoxymethoxy-5-methyl-1-benzoyloxybenzene was dissolved in 200 ml of methanol, and the solution was stirred at room temperature for 1 hour, while adding dropwise 60 ml of 10% aqueous potassium hydroxide solution. After completion of the reaction, the solvent was removed by distillation under reduced pressure. The residue was added to 150 ml of water, neutralized with 10% aqueous hydrochloric acid solution, and extracted with 200 ml of diethyl ether. The solvent was removed by distillation under reduced pressure, and the residue was subjected to silica gel chromatography, which afforded 17.4 g of 3-chloro-4-methoxymethoxy-5-methylphenol (96% yield).

To a mixture of 10 g of 3-chloro-4-methoxymethoxy-5-methylphenol, 7 g of potassium carbonate and 100 ml of N,N-dimethylformamide was added dropwise a solution of 8 g of 1,1,3-trichloro-1-propene dissolved in 30 ml of N,N-dimethylformamide, while stirring at room temperature. After stirring at room temperature for 12 hours, the reaction mixture was poured into ice-water, and extracted twice with 200 ml of diethyl ether. The combined ether layer was washed with water, dried with anhydrous magnesium sulfate, and concentrated. The residue was subjected to silica gel chromatography, which afforded 14.1 g of 3-chloro-4-methoxymethoxy-5-methyl-1-(3,3-dichloro-2-propenyloxy)benzene (91% yield).

Then, 14.1 g of 3-chloro-4-methoxymethoxy-5-methyl-1-(3,3-dichloro-2-propenyloxy)benzene was dissolved in 100 ml of 80% aqueous acetic acid solution, followed by heating under reflux with stirring for 1 hour. After completion of the reaction, the reaction mixture was mixed with 200 ml of water, and extracted twice with 200 ml of diethyl ether. The combined ether layer was washed with water, dried with anhydrous magnesium sulfate, and concentrated. The residue was subjected to silica gel chromatography, which afforded 11.3 g of 2-chloro-6-methyl-(3,3-dichloro-2-propenyloxy)phenol (93% yield), m.p. 70.0° C.

The following is a production example for the intermediate compounds of general formula [XIII].

Reference Production Example 3 Production of 3,5-dichloro-4-(3-bromopropyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene

A reaction vessel was charged with 10.6 g of 1,3-dibromopropane, 5.53 g of potassium carbonate and 100 ml of N,N-dimethylformamide, to which a solution of 30.5 g of 2,6-dichloro-4-(3,3-dichloro-2-propenyloxy)phenol dissolved in 40 ml of N,N-dimethylformamide was slowly added dropwise. After stirring at room temperature for 24 hours, the reaction mixture was poured into water, and extracted twice with 150 ml of diethyl ether. The combined ether layer was washed with water, dried with anhydrous magnesium sulfate, and concentrated to obtain a crude product. The crude product was subjected to silica gel chromatography, which afforded 11.1 g of 3,5-dichloro-4-(3-bromopropyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene (77% yield), n_(D) ^(24.0) 1.5693.

The following are formulation examples in which “parts” are by weight and the present compounds are designated by the corresponding compound numbers as described above.

Formulation Example 1 Emulsifiable Concentrates

Ten parts of each of the present compounds (1) to (70) are dissolved in 35 parts of xylene and 35 parts of N,N-dimethylformamide, to which 14 parts of polyoxyethylene styrylphenyl ether and 6 parts of calcium dodecylbenzenesulfonate are added, and the mixture is well stirred to give a 10% emulsifiable concentrate of each compound.

Formulation Example 2 Wettable Powders

Twenty parts of each of the present compounds (1) to (70) are added to a mixture of 4 parts of sodium lauryl sulfate, 2 parts of calcium lignin sulfonate, 20 parts of synthetichydrated silicon oxide fine powder and 54 parts of diatomaceous earth, and the mixture is stirred with a mixer to give a 20% wettable powder of each compound.

Formulation Example 3 Granules

Five parts of each of the present compounds (1) to (70), 5 parts of synthetic hydrated silicon oxide fine powder, 5 parts of sodium dodecylbenzenesulfonate, 30 parts of bentonite and 55 parts of clay are mixed, and the mixture is well stirred. Then, a suitable amount of water is added to the mixture, which is further stirred, granulated with a granulator and then air-dried to give a 5% granule of each compound.

Formulation Example 4 Dusts

One part of each of the present compounds (1) to (70) is dissolved in a suitable amount of acetone, to which 5 parts of synthetichydrated silicon oxide fine powder, 0.3 part of PAP and 93.7 parts of clay are added, and the mixture is stirred with a mixer. The removal of acetone by evaporation gives a 1% dust of each compound.

Formulation Example 5 Flowables

Twenty parts of each of the present compounds (1) to (70) are mixed with 1.5 parts of sorbitan trioleate and 28.5 parts of an aqueous solution containing 2 parts of polyvinyl alcohol, and the mixture is pulverized into fine particles having a particle size of not more than 3 μm with a sand grinder, to which 40 parts of an aqueous solution containing 0.05 part of xanthan gum and 0.1 part of aluminum magnesium silicate are added and then 10 parts of propylene glycol are added. The mixture is stirred to give a 20% water-based suspension of each compound.

Formulation Example 6 Oil Solutions

First, 0.1 part of each of the present compounds (1) to (70) is dissolved in 5 parts of xylene and 5 parts of trichloroethane. Then, the solution was mixed with 89.9 parts of deodorized kerosine to give a 0.1% oil solution of each compound.

Formulation Example 7 Oil-based Aerosols

First, 0.1 part of each of the present compounds (1) to (70), 0.2 part of tetramethrin, 0.1 part of d-phenothrin, and 10 parts of trichloroethane are dissolved in 59.6 parts of deodorized kerosine, and the solution is put in an aerozol vessel. Then, the vessel is equipped with a valve, through which 30 parts of a propellant (liquefied petroleum gas) are charged under increased pressure to give an oil-based aerosol of each compound.

Formulation Example 8 Water-based Aerosols

An aerosol vessel is filled with 50 parts of pure water and a mixture of 0.2 part of each of the present compounds (1) to (70), 0.2 part of d-allethrin, 0.2 part of d-phenothrin, 5 parts of xylene, 3.4 parts of deodorized kerosine and 1 part of an emulsifier [ATMOS 300 (registered trade name by Atlas Chemical Co.)]. Then, the vessel is equipped with a valve, through which 40 parts of a propellant (liquefied petroleum gas) are charged under pressure to give a water-based aerosol of each compound.

Formulation Example 9 Mosquito-coils

First, 0.3 g of each of the present compounds (1) to (70) is mixed with 0.3 g of d-allethrin, and the mixture is dissolved in 20 ml of acetone. The solution is uniformly mixed with 99.4 g of a carrier for mosquito-coils (prepared by mixing Tabu powder, pyrethrum marc powder and wood flour in the ratio of 4:3:3) under stirring. The mixture is well kneaded with 120 ml of water, molded and dried to give a mosquito-coil of each compound.

Formulation Example 10 Electric Mosquito-mats

First, 0.4 g of each of the present compounds (1) to (70), 0.4 parts of d-allethrin and 0.4 g of pipenyl butoxide are dissolved in acetone to have a total volume of 10 ml. Then, 0.5 ml of the solution is uniformly absorbed in a substrate for electric mosquito-mats having a size of 2.5 cm×1.5 cm×0.3 cm (prepared by forming a fibrillated mixture of cotton linter and pulp into a sheet) to give an electric mosquito-mat of each compound.

Formulation Example 11 Heating Smoke Formulations

First, 100 mg of each of the present compounds (1) to (70) is dissolved in a suitable amount of acetone. Then, the solution is absorbed in a porous ceramic plate having a size of 4.0 cm×4.0 cm×1.2 cm to give a heating smoke formulation of each compound.

Formulation Example 12 Poison Baits

First, 10 mg of each of the present compounds (1) to (70) is dissolved in 0.5 ml of acetone, and the solution is uniformly mixed with 5 g of solid bait powder for animals (Breeding Solid Feed Powder CE-2, trade name by Japan Clea Co., Ltd.). Then, the removal of acetone by air drying gives a 0.5% poison bait of each compound.

The following test examples demonstrate that the present compounds are useful as an active ingredient of insecticidal/acaricidal agents. In these test examples, the present compounds are designated by the corresponding compound numbers as described above and the compounds used for comparison are designated by the corresponding compound symbols as shown in Table 47.

TABLE 47 Compound Chemical structure Remarks (A)

Compound disclosed in JP-A 48-86835/1973, page 23 (B)

Compound disclosed in JP-A 49-1526/1974, page 22

Test Example 1 Insecticidal Test Against Spodoptera litura

A 200-fold dilution containing an active ingredient at 500 ppm, which had been prepared by diluting with water an emulsifiable concentrate of the test compound obtained according to Formulation Example 1, was absorbed at a volume of 2 ml in 13 g of an artificial diet for Spodoptera litura, which had been prepared in a polyethylene cup having a diameter of 11 cm. Ten fourth-instar larvae of Spodoptera litura were set free in the cup. After 6 days, the survival of larvae was examined to determine the mortality. The test was conducted in duplicate.

As a result, it was found that the present compounds (1), (2), (5)-(7), (9)-(11), (14), (16)-(18), (20)-(26), (28)-(37) and (39)-(50) exhibited the mortality of 80% or more. In contrast, both compounds (A) and (B) for comparison exhibited the mortality of 0%.

Test Example 2 Test against Tetranychus urticae Koch

Ten female adults of Tetranychus urticae Koch per one leaf were allowed to parasitize to a potting bean at the primary leaf stage harvested for 7 days after seeding, and these pots were placed in a thermostated room at 25° C. After 6 days, a chemical solution containing an active ingredient at 500 ppm, which had been prepared by diluting with water an emulsifiable concentrate of the test compound obtained according to Formulation Example 1, was sprayed at a volume of 15 ml over each pot on a turntable. At the same time, 2 ml of the same solution was drenched in the soil. After 8 days, the degree of damage on the respective plants caused by Tetranychus urticae Koch was examined. The effects were determined according to the following criteria:

−: Damage is scarcely observed.

+: Damage is slightly observed.

++: Damage is observed at the same level as in the non-treated field.

As a result, it was found that the present compounds (1), (7), (10), (15), (30), (32) and (33) were evaluated as “−” or “+”. In the contrast, both compounds A and B for comparison were evaluated as “++”.

Test Example 3 Insecticidal Test Against Heliothis virescens

A dilution containing an active ingredient at 100 ppm, which had been prepared by diluting with water an emulsifiable concentrate of the test compound obtained according to Formulation Example 1, was incorporated at a volume of 0.2 ml in an artificial diet. A second-instar larva of H. virescens was given the diet and bred in a plastic vessel. Ten insects were used by each treatment. After 6 days, the mortality was determined.

As a result, it was found that the present compounds (36), (42) and (43) exhibited the mortality of 80% or more. In contrast, both compounds (A) and (B) for comparison exhibited the mortality of 0%.

Test Example 4 Insecticidal Test Against Plutella xylostella

A chemical solution containing an active ingredient at 50 ppm, which had been prepared by diluting an emulsifiable concentrate of the test compound obtained according to Formulation Example 1 with water containing spreading agent RINOU (Nihon Nouyaku K.K.) to a degree such that the spreading agent had been 1000-fold diluted, was sprayed at a volume 25 ml over each pot of a potting cabbage at the five leaf stage. The treated plants were air dried, on which ten third-instar larvae of Plutella xylostella were set free. After 4 days, the mortality was determined.

As a result, it was found that the present compounds (36), (37), (42) and (45)-(48) exhibited the mortality of 80% or more. In contrast, both compounds (A) and (B) for comparison exhibited the mortality of 0%.

INDUSTRIAL APPLICABILITY

The present compounds have excellent insecticidal/acaricidal activity, so that they are satisfactorily effective for the control of noxious insects, mites and ticks. 

What is claimed is:
 1. A dihalopropene compound of the general formula:

wherein Z is oxygen, sulfur or NR⁴ and wherein R⁴ is hydrogen or C₁-C₃ alkyl; Y is oxygen, sulfur or NH; X's are independently chlorine or bromine; R², R³ and R¹⁰ are independently halogen, C₁-C₃ haloalkyl or C₁-C₃ alkyl; t is an integer of 0 to 2; and R¹ is Q₁, Q₂, Q₃, Q₄, Q₅, Q₆ or Q₇ of the general formula:

wherein A is an optionally substituted 5-membered heterocyclic ring group containing 2, 3 or 4 nitrogen atoms and 1 or 2 carbon atoms; B is oxygen, S(O)_(q), NR⁹, C(═G¹)G² or G¹C(═G²); q is an integer of 0 to 2; R⁹ is hydrogen, acetyl or C₁-C₃ alkyl; G¹ and G² are independently oxygen or sulfur; R⁵, R⁶, R⁷, R¹¹ and R¹² are independently hydrogen, C₁-C₃ alkyl or trifluoromethyl; R¹³ and R¹⁴ are independently hydrogen, C₁-C₃ alkyl, trifluoromethyl or halogen; p is an integer of 0 to 6; and s is an integer of 1 to
 6. 2. The dihalopropene compound according to claim 1, wherein A is a 5-membered heterocyclic ring group selected from triazolyl, tetrazolyl or thiadiazolyl and optionally substituted with (R⁸)_(r), wherein R⁸ is halogen, nitro, cyano, C₁-C₄ alkyl, C₁-C₃ haloalkyl, C₁-C₄ alkoxy, C₁-C₃ haloalkoxy, C₁-C₃ alkylthio, C₁-C₃ haloalkylthio, C₁-C₂ alkylsulfinyl, C₁-C₂ alkylsulfonyl, C₁-C₂ haloalkylsulfinyl, C₁-C₂ haloalkylsulfonyl, C₂-C₄ alkenyl, C₂-C₄ haloalkenyl, C₂-C₄ alkynyl, C₂-C₄ haloalkynyl, amino, dimethylamino, acetamido, acetyl, haloacetyl, formyl, carboxyl, methoxycarbonyl, C₃-C₆ cycloalkyl, (C₁-C₂ alkyl)aminocarbonyl or [di(C₁-C₂ alkyl)amino]carbonyl, or R⁸ is phenyl, benzyl, phenoxy, benzyloxy or pyridyloxy, each of which is optionally substituted with halogen, C₁-C₄ alkyl, C₁-C₃ haloalkyl, C₁-C₄ alkoxy or C₁-C₃ haloalkoxy; and r is an integer of 0 to
 7. 3. The dihalopropene compound according to claim 1, wherein R² and R³ are independently halogen or C₁-C₃ alkyl; and t is
 0. 4. The dihalopropene compound according to claim 1, wherein R² and R³ are independently chlorine, bromine, methyl, ethyl or isopropyl; and t is
 0. 5. The dihalopropene compound according to claim 1, wherein R² and R³ are both chlorine; and t is
 0. 6. The dihalopropene compound according to claim 1, wherein R² is chlorine; R³ is methyl; and t is
 0. 7. The dihalopropene compound according to claim 1, wherein R² is ethyl; R³ is methyl; and t is
 0. 8. The dihalopropene compound according to claim 1, wherein R² and R³ are both bromine; and t is
 0. 9. The dihalopropene compound according to claim 1, wherein R² and R³ are both ethyl; and t is
 0. 10. The dihalopropene compound according to claim 1, wherein R² and R³ are independently halogen or C₁-C₃ alkyl; t is 1 or 2; and R¹⁰ is halogen or C₁-C₃ alkyl.
 11. The dihalopropene compound according to claim 1, wherein R² and R³ are independently halogen or C₁-C₃ alkyl; t is 1 or 2; and R¹⁰ is halogen.
 12. The dihalopropene compound according to claim 1, wherein Y and Z are both oxygen.
 13. The dihalopropene compound according to claim 4, wherein Y and Z are both oxygen.
 14. The dihalopropene compound according to claim 1, wherein R¹ is Q₁.
 15. The dihalopropene compound according to claim 1, wherein R¹ is Q₂.
 16. The dihalopropene compound according to claim 13, wherein R¹ is Q₃.
 17. The dihalopropene compound according to claim 13, wherein R¹ is Q₄.
 18. The dihalopropene compound according to claim 13, wherein R¹ is Q₅.
 19. The dihalopropene compound according to claim 13, wherein R¹ is Q₆.
 20. The dihalopropene compound according to claim 13, wherein R¹ is Q₇.
 21. An insecticidal/acaricidal agent comprising the dihalopropene compound according to claim 1 as an active ingredient. 